Stem Cells - Potential to treat all Dieseases

Contents

1 Properties of Stem Cells.

2. Embryonic Stem Cells

3 Adult Stem Cell

4 Lineage
5.Uses in research

6. Clinical Importance & Applications
7 Reprogramming of Stem Cells
8 Controversies in Stem Cells research.
9 Ethical, Social & Legal issues In Stem Cells Research.

10 Stem cell funding & policy debate in the US

11 Key research in Stem Cells.

Stem cell

Stem cells are Cells found in most, if not all, multi-cellular organisms. They are characterized by the ability to renew themselves Mitotic cell Division and differentiating into a diverse range of specialized cell types. Research in the stem cell field grew out of findings by Canadian scientists Ernest A. McCulloch and James E. Till in the 1960s. The two broad types of mammalian stem cells are: embryonic stem cells that are found in blastocysts, and adult stem cells that are found in adult tissues. In a developing embryo, stem cells can differentiate into all of the specialized embryonic tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of regenerative organs, such as blood, skin or intestinal tissues.
As stem cells can be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture, their use in medical therapies has been proposed. In particular, embryonic cell lines, autologous embryonic stem cells generated through therapeutic cloning, and highly plastic adult stem cells from the umbilical cord blood or bone marrow are touted as promising candidates.

Properties of stem cells
The classical definition of a stem cell requires that it possess two properties:
Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
Potency - the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent - to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells.

Potency definitions
Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.
Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.
Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. These cells can differentiate into embryonic and extraembryonic cell types.
Pluripotent stem cells are the descendants of totipotent cells and can differentiate into cells derived from any of the three germ layers.
Multipotent stem cells can produce only cells of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).
Unipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells).

Identifying stem cells
The practical definition of a stem cell is the functional definition - the ability to regenerate tissue over a lifetime. For example, the gold standard test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.
Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, where single cells are characterized by their ability to differentiate and self-renew. As well, stem cells can be isolated based on a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells.

Embryonic stem cells
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos.[6] A blastocyst is an early stage embryo—approximately four to five days old in humans and consisting of 50–150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.
Nearly all research to date has taken place using mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia Inhibitory Factor (LIF). Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic Fibroblast Growth Factor (bFGF or FGF-2). Without optimal culture conditions or genetic manipulation, embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the presence of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and SOX2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency. The cell surface antigens most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.
After nearly ten years of research, there are no approved treatments or human trials using embryonic stem cells. ES cells, being pluripotent cells, require specific signals for correct differentiation - if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face. Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.

Adult stem cells
Stem cell division and differentiation. A - stem cell; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation
The term adult stem cell refers to any cell which is found in a developed organism that has two properties: the ability to divide and create another cell like itself and also divide and create a cell more differentiated than itself. Also known as somatic (from Greek Σωματικóς, "of the body") stem cells and germline (giving rise to gametes) stem cells, they can be found in children, as well as adults.
Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood. A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential. In mice, pluripotent stem cells are directly generated from adult fibroblast cultures.
Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.).
Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants. Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses. The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, because in some instances adult stem cells can be obtained from the intended recipient, (an autograft) the risk of rejection is essentially non-existent in these situations. Consequently, more US government funding is being provided for adult stem cell research.

Lineage
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.
An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals dpp and adherins junctions that prevent germarium stem cells from differentiating.
The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include several transcription factors including the oncogene c-Myc. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent. However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy.
Treatments
Medical researchers believe that stem cell therapy has the potential to dramatically change the treatment of human disease. A number of adult stem cell therapies already exist, particularly bone marrow transplants that are used to treat leukemia. In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety of diseases including cancer, Parkinson's disease, spinal cord injuries, Amyotrophic lateral sclerosis and muscle damage, amongst a number of other impairments and conditions. However, there still exists a great deal of social and scientific uncertainty surrounding stem cell research, which could possibly be overcome through public debate and future research, and further education of the public.
Stem cells, however, are already used extensively in research, and some scientists do not see cell therapy as the first goal of the research, but see the investigation of stem cells as a goal worthy in itself.



Uses in Research

Much is left to be discovered and understood in all aspects of human biology. What has
been frequently lacking are the tools necessary to make the initial discoveries, or to apply
the knowledge of discoveries to the understanding of complex systems. These are some
of the larger problems in basic and clinical biology where the use of stem cells might be
the key to understanding.

A new window on human developmental biology.
The study of human developmental
biology is particularly constrained by practical and ethical limitations. Human ES cells
may allow scientists to investigate how early human cells become committed to the major
lineages of the body; how these lineages lay down the rudiments of the body’s tissues and
organs; and how cells within these rudiments differentiate to form the myriad functional
cell types which underlie normal function in the adult. The knowledge gained will impact
many fields. For example, cancer biology will reap an especially large reward because it is now understood that many cancers arise by perturbations of normal developmental
processes. The availability of human ES cells will also greatly accelerate the understanding
of the causes of birth defects and thus lead directly to their possible prevention.

Models of human disease that are constrained by current animal and cell culture models.
Investigation of a number of human diseases is severely constrained by a lack of in vitro
models. A number of pathogenic viruses including human immunodeficiency virus and
hepatitis C virus grow only in human or chimpanzee cells. ES cells might provide cell
and tissue types that will greatly accelerate investigation into these and other viral
diseases. Current animal models of neurodegenerative diseases such as Alzheimer’s
disease give only a very partial representation of the disease’s process.

Transplantation.
Pluripotent stem cells could be used to create an unlimited supply of
cells, tissues, or even organs that could be used to restore function without the requirement for toxic immunosuppression and without regard to tissue matching compatibility.
Such cells, when used in transplantation therapies, would in effect be suitable for
“universal” donation. Bone marrow transplantation, a difficult and expensive procedure
associated with significant hazards, could become safe, cost effective, and be available
for treating a wide range of clinical disorders, including aplastic anemia and certain
inherited blood disorders. This would be especially important in persons who lost marrow
function from toxic exposure, for example to radiation or toxic agents. Growth and
transplant of other tissues lost to disease or accident, for example, skin, heart, nervous
system components, and other major organs, are foreseeable.


Gene Therapy.
In gene therapy, genetic material that provides a missing or necessary
protein, or causes a clinically-relevant biochemical process, is introduced into an organ
for a therapeutic effect. For gene-based therapies (specifically, those using DNA sequences),
it is critical that the desired gene be introduced into organ stem cells in order to
achieve long-term expression and therapeutic effect. Although techniques for delivering
the therapeutic DNA have been greatly improved since the first gene therapy protocol
almost 10 years ago, there are as yet no bona fide successes. Besides delivery problems,
loss of expression or insufficient expression is an important limiting factor in successful
application of gene therapy and could be overcome by transferring genes into stem cells
(which presumably will then differentiate and target correctly).


Drug discovery
Stem cells have numerous applications in drug discovery. They are important for understanding differentiation pathways, for identifying factors needed to manipulate cell lineages, for improving screening assays, and for identifying disease targets. The production of stem-cell-derived human hepatocytes will have an immediate impact on toxicology and metabolism studies.

Study human development
Stem cells could be used to study early events in human development and how cells differentiate and function. This may help researchers find answers as to why some cells become cancerous and how some genetic diseases develop, which may lead to clues as to how they may be prevented.

Testing of new drugs
Stem cells grown in the laboratory may be useful for testing drugs and chemicals before they are trialled in people. The cells could be directed to differentiate into the cell types that are important for screening that drug. These cells may be more likely to mimic the response of human tissue to the drug being tested, compared to some of the animal models currently being used. This may make drug testing safer, cheaper and more ethically acceptable to those who oppose the use of animals in pharmaceutical testing.

The Clinical Potentials for Stem Cell Products

The economic and psychological tolls of chronic, degenerative, and acute diseases in the
United States are enormous. It has been estimated that up to 128 million people suffer
from such diseases; thus, virtually every citizen is effected directly or indirectly.8 The
total costs of treating diabetes, for example is approaching $100 billion in the United
States alone.9 As more research takes place, the developmental potential of different
kinds of stem cells will become better understood. As the science is understood now,
adult stem cells are limited in their potential to differentiate. Embryonic germ cells have
a great differentiation capacity, and embryonic stem cells are thought to be able to
differentiate into almost any tissue. Thus, different types of stem cells could have
different applications. Below is a discussion of potential stem cell applications.


Type 1 Diabetes in Children.
Type 1 diabetes is an autoimmune disease characterized by
destruction of insulin producing cells in the pancreas. Current efforts to treat these
patients with human islet transplantation in an effort to restore insulin secretory function
(obtained from human pancreas) are limited severely by the small numbers of donated
pancreas available each year combined with the toxicity of immunosuppressive drug
treatments required to prevent graft rejection.10 Pluripotent stem cells, instructed to
differentiate into a particular pancreatic cell called a beta cell, could overcome the
shortage of therapeutically effective material to transplant. They also afford the opportunity
to engineer such cells to effectively resist immune attack as well as graft rejection.

Stem cell treatment of Diabetes mellitus type 1 & 2
Diabetes type 1
The autoimmune reaction of the body to the pancreatic beta cells in the islets of Langerhans and the resulting destruction of these beta cells, cause an immediate insuline deficiency, resulting in type 1 diabetes.
Diabetes mellitus type 1 is a degenerative disease, which is traditionally treated using insuline injections. These injections replace the missing hormone, but the complications can be far-reaching. Hyperglycemia is a common contributor to a number of complications like
Heart and vascular diseases
Eye and kidney complaints
Poor vascularisation
Damage to nerve cells (neuropathy)
Diabetic feet
High susceptibility for infections
Erectile penile dysfunction
Diabetes type 2
Type 2 diabetes used to be known as maturity onset, or non-insulin dependent diabetes. Although type 2 diabetes typically affects individuals over the age of 40, today it occurs at an increasingly younger age, especially in people who have a family history of diabetes.
Diabetes mellitus type 2 is by far the most common form, affecting 85 - 90% of all people with diabetes. Experts estimate that nearly one-third of people who have type 2 diabetes don't even know it. If the condition is left uncontrolled, the consequences (like with diabetes type 1) can be life threatening.
Diabetes Mellitus treatment
The innovative adult stem cell therapy with autologous stem cells (originating from your own body and being reimplanted) is unique in Europe and fights type 1 and type 2 diabetes at its roots, reducing hyperglycemia and consequently the above mentioned complications.
The stem cells are first collected from a patient’s bone marrow, extracted from the hipbone (iliac crest) then implanted back into the body days later. Prior to re-implantation of the cells, the bone marrow is processed in one of our labs, where the quantity and quality of the stem cells is also checked.
These re-injected stem cells have the potential to transform into multiple types of cells and are capable of regenerating damaged cells such as pancreatic beta cells. Our innovative stem cell treatments use the self-healing potential of each patient’s own body to stimulate regeneration or repair. And since the implanted cells are autologous, there is practically no chance an immune reaction will follow.



Nervous System Diseases
Many nervous system diseases result from loss of nerve cells.
Mature nerve cells cannot divide to replace those that are lost. Thus, without a “new”
source of functioning nerve tissue, no therapeutic possibilities exist. In Parkinson’s
disease, nerve cells that make the chemical dopamine die. In Alzheimer’s disease, cells
that are responsible for the production of certain neurotransmitters die. In amyotrophic
lateral sclerosis, the motor nerve cells that activate muscles die. In spinal cord injury,
brain trauma, and even stroke, many different types of cells are lost or die. In multiple
sclerosis, glia, the cells that protect nerve fibers are lost.11 Perhaps the only hope for
treating such individuals comes from the potential to create new nerve tissue restoring
function from pluripotent stem cells.
Remarkably, human clinical experiments have demonstrated the potential effectiveness of
this approach to treatment. Parkinson’s patients have been treated by surgical implantation
of fetal cells into their brain with some benefit. Although not completely effective,
perhaps owing to lack of sufficient numbers of dopamine secreting cells, similar experiments
using appropriately differentiated stem cells should overcome those obstacles.12
More complex experiments have already been successfully conducted in rodent models
of Parkinson’s.13 Similar approaches could be developed to replace the dead or dysfunctional
cells in cortical and hippocampal brain regions that are affected in patients
with Alzheimer’s.


Parkinson’s Disease
Parkinson’s Disease involves the loss of cells which produce the neurotransmitter dopamine. The first double-blind study of fetal cell transplants for Parkinson’s Disease reported survival and release of dopamine from the transplanted cells and a functional improvement of clinical symptoms.4 However, some patients developed side effects, which suggested that there was an oversensitization to or too much dopamine. Although the unwanted side effects were not anticipated, the success of the experiment at the cellular level is significant. Again, further studies are needed and ongoing. Over 250 patients have already been transplanted with human fetal tissue


Alzheimer's disease
Alzheimer's disease is the most common form of senile dementia. It is typically associated with a slow but progressive loss of nerve cells and nerve cell contacts. The onset of the disease is insidious, and the first symptoms to manifest are impaired memory and orientation.
As the disease progresses, the sufferer's mental faculties deteriorate and, after a few years, patients require help to perform everyday tasks and are no longer able live on their own. One particularly disturbing aspect of this stage of the disease for family and friends is that the patient often doesn't recognize close relatives or perhaps even their partner. People with Alzheimer's disease also gradually lose their personality.
It is not known what causes Alzheimer's disease, although the brains of Alzheimer's patients do demonstrate typical microscopic changes: Extracellular protein depositions –called amyloid plaques– and fibrous intracellular protein aggregations –called neurofibrillar tangles. It seems impossible to cure Alzheimer's disease because dead nerve cells cannot be regenerated.

Alzheimer's disease treatment
The stem cells are first collected from a patient’s bone marrow, extracted from the hipbone (iliac crest) then implanted back into the body days later. Prior to re-implantation of the cells, the bone marrow is processed in one of our labs, where the quantity and quality of the stem cells is also checked.
These re-injected stem cells have the potential to transform into new cells; rejuvenating or replacing damaged tissue and/or nerves.
The goal of the treatment is to slow down or stop the regression of the symptoms of Alzheimer's disease.


Stem cells for improving beauty
a. Natural hair growth is attained for bald men.b. Using stem cells, we can develop tissue and specialized cell types, that enables to replace the damaged body parts.c. Breast cancer patients, (whose breast is removed) can have natural replacement after mastectomy. Thus, currently used artificial breast implants (Silicone & Saline implants) become outdated. This is possible by deriving stem cells from one's own fat and creating a durable piece of replacement tissue.d. Fat derived stem cells can be used for breast enlargement.e. Stem cell derived from the body can also be used for face rejuvenation, warding of wrinkles, fine lines. f. With advances in stem cell therapy, large scale skin replacement grafts, would be possible. This would bring a great relief to chronic wound patients and those suffering from burns.
However, at this point of time, researchers predict that the fruits of stem cell therapy, would be enjoyed by the next generation. \

Hair Loss & stem cells
Baldness is probably the one thing that causes men more anxiety than anything else in their life. Now, scientists believe they may have found a new way to reverse baldness and treat conditions like alopecia. Scientists have identified stem cells or master cells in the hair follicles of mice. They found that these cells grow into hair follicles and produce hair when transplanted into skin. George Cotsarelis, Assistant Professor of dermatology from the University of Pennsylvania, said that the study could lead to new ways of treating hair loss in humans through drugs or surgery. "This may lead to a new type of tissue engineering for treating baldness - for example, isolating hair follicle stem cells from the scalp and reconstituting hair follicles in bald areas," Dr Cotsarelis said. "I can't predict the future but this type of research certainly opens new avenues for developing new treatments for baldness." The study, published in the journal Nature Biotechnology, isolated the stem cells within the bulbous follicle at the base of a hair shaft. Sometimes these follicles go into a permanent resting phase, halting hair regeneration. When the researchers transplanted the stem cells into the skin of other mice, hair follicles began to re-grow within four weeks.
Receding hairlines and the arrival of the bald patch are feared by men around the globe. Hair may start to disappear from the temples and the crown of the head at any time. For some men this process starts as early as the later teenage years, for most it happens in the late 20s and early 30s. Initially it may just be a little thinning that's noticed. Then, the absence of hair allows more of the scalp to become visible. Some men are not troubled by this process at all. Others, however, suffer great emotional distress associated with a lack of self-confidence and sometimes depression. In male pattern baldness, which is hereditary, the hair is usually lost at the temples and the crown. This happens because an over-sensitivity of the hair follicle to normal levels of testosterone switches the hair loss gene on. Not every hair follicle has this gene which is why some hair falls out whilst other hair doesn't. Other causes of hair-loss that are usually reversible include; iron deficiency anaemia; under-active thyroid; fungal scalp infection; some prescribed medicines;and stress. Scientists have long-suspected that hair follicles contained stem cells. However, it has proved difficult to isolate these cells in humans. This latest study raises hopes that they can now track these genes and identify stem cells in human hair follicles. "Ultimately, these findings provide potential targets for the treatment of hair loss and other disorders of skin and hair," the researchers wrote. While the discovery could lead to new treatments for baldness and conditions like alopecia, the researchers believe it may also help burn victims. "One problem with a burn is that the wound is never covered with hair follicles," said Dr Cotsarelis. "These cells have that capability so if we can isolate them and seed them onto a wound we can constitute skin that is more normal than currently possible."
Scientists at University of Illinois in Chicago have told a conference that they have stimulated stem cells from a human donor to develop into the fatty tissue of the skin. Jeremy Mao, professor of tissue engineering, said that female cancer patients undergoing a mastectomy may have their breast replacements grown from their own cells for reconstructive surgery.In experiments with mice, skin replacement pieces were grown and could be guided to grow into desired shapes. “After four weeks we found the implant was indeed generating adipose tissue from stem cells, and that its shape and dimensions were well retained,”
“The technique is also applicable for other soft tissue, facial tissue such as the lips and so on. The great thing about the stem cell-derived implant is that its shape and dimensions were retained,” he told the conference of the American Association for the Advancement of Science in Washington DC.
Barrandon was part of a French research team who reported in the scientific journal Cell that stem cells could be used to generate skin containing hair and sebaceous glands in mice. But at that time it was unclear whether the stem cells in hair follicles were true stem cells, capable of long-term renewal, or multipotent progenitor cells that would not permanently engraft in the follicle.
In the current PNAS study, the Swiss researchers have answered that question, using rat whisker hair follicles to demonstrate that the clonogenic keratinocytes in hair follicles are true stem cells.
Barrandon's group isolated stem cells from rat whisker follicles, labelled them, and grew them in culture for 140 generations. They then implanted progeny cells into the skin of newborn mice whose hair follicles were just being formed. This skin was then grafted onto athymic (nude) mice. Some cells were incorporated into developing follicles, but other follicles were completely made up of labelled cells. Each progeny cell contributed to the formation of eight different types of cell in the follicle, including those of the outer root sheath, inner root sheath, the hair shaft, the sebaceous gland and the epidermis.
After 125 days, a biopsy was taken from the graft, and labelled stem cells were isolated, subcloned, cultivated and then once again transplanted. The rat whisker stem cells participated again in forming all the cell types needed to form the hair follicle and sebaceous glands, resulting in hair bulbs that underwent repeated normal phases of growth, rest and regeneration. The fact that the transplanted cells participate in the hair cycle over long periods of time shows that they are true multipotent stem cells and not progeniture cells.
"With the progeny of a single stem cell, it would be theoretically possible to generate the complete hair bulb of a human being, and one that would last for years," explains Barrandon.
The ability of the stem cells in hair follicles to repeatedly regenerate all the different cell types of the follicle and sebaceous glands has important implications for regenerative medicine. The method could one day be used to regenerate hair on patients with severe burns. This study is a logical complement to other work in Barrandon's Laboratory of Stem Cell Dynamics, recognized for research into the reconstruction of injured tissues and organs.
After purifying a sufficient amount of these cells, both groups used gene chips to find which genes were switched on in the stem cells. For the first time, this provides a signature that researchers can use to identify the same cells in humans.
Tiny colorless hairs
It also suggests many new genes that might control hair production. Male pattern baldnesses, for example, results when follicles start producing tiny, colourless hairs that are nearly invisible. But the underlying cause for this switch from thick to thin hair production is not known. Cotsarelis says that with these cells in hand, it might eventually be possible to screen for drugs that will reverse this balding process.
Stem cells are special cells that act as a repair system of body tissues like intestine, hair follicles, blood capillaries, stomach etc. Stem cells are found in all regenerative organs, that is, organs that regenerates themselves after specific time period. There are two types, embryonic and adult stem cells. Stem cells multiply through meiotic cell division. Stem cells can be transferred to damaged tissue for regeneration. Conclusively, stem cells are essential for regeneration of tissues of various body organs.
Hair follicles are tiny tubular cavities made up of epithelial tissues. For healthy hair growth, each hair follicles undergoes its growth cycle. At some time, most of the hair follicles are resting period and soon enters the growth phase again. But in most cases, hair follicles do not get into growth phase and get destroyed. At this stage hair loss begins, and you notice hair thinning that laster leads to complete baldness. Stem cells are responsible to stimulate the hair follicles to regenerate and enter into growth phase after resting phase. Studies show transplantation of stem cells promotes hair growth.
A study was conducted at the university of Pennsylvania School of Medicine for isolating the stem cells for hair growth. According to researchers, stem cells near the follicle bulb are responsible for healthy growth of hair follicles and hair shafts. To test the theory, they done a experiment on mice. They isolated the stem cells from hair follicles of healthy and normal growing mice and transferred them to an adult mice having poor hair growth.

Skin replacement
Many people only think about hair follicle activity when they need a haircut or shave. However, recent research indicates that hair follicle epithelial cells also play a key role in skin stem cell biology. In a recent issue of Cell, Taylor et al. reported the use of an elegant double-labeling technique to trace the distribution and proliferative activity of hair follicle epithelial cells over long periods in newborn and wounded adult mice1. The authors demonstrated that progeny of epithelial cells, located in the upper follicle bulge, not only incorporate into hair-forming elements low down in the follicle, but also move up and out from the follicle outer root sheath (ORS) into the epidermis of adjoining skin.This is new experimental evidence that the follicular stem cell population has a dual function in making hair and contributing to skin epidermis. It is important because identifying skin stem cells and learning about the processes that regulate these stem cells will improve the prospects for skin replacement, skin-based tissue engineering and treatments for skin cancers. These findings may also aid skin-based gene therapies, as recent studies in hair follicle transfection have demonstrated that progenitor cells are selectively targeted by a lipid-based delivery system2.Follicle epithelium has long been recognized as a source of epidermis in healing wounds. Indeed, clinically, this phenomenon underpins autologous split-thickness grafting, a process in which the epidermis and some underlying dermis is removed from a healthy skin site and grafted to a defective region. At the donor site, the replacement epidermis comes from remnants of hair follicles and gland epithelium in the dermis. The findings of Taylor et al.1 indicate that epidermis can be produced by hair follicles in undamaged newborn skin, and that stem cell progeny move horizontally from the follicle, a process that the authors have demonstrated to occur in other systems such as eye corneal epithelium.Although stem cells are permanently self-replicating, they are generally slow cycling. Conventionally, they are thought to give rise to a transient amplifying cell population, with limited self-renewal, to increase numbers of differentiated cells. When researchers first proposed that slow-cycling, label-retaining cells in the 'bulge' were the principal follicle stem cells3, several questions remained unanswered. One challenge was to locate stem cells in adult human follicles, since these follicles lack an anatomically well-defined bulge region. An indirect approach has been to use molecular markers, such as l integrin, to identify follicle stem cells. Cells that express high levels of l integrin had been previously identified as stem cells in skin epidermis. Direct evidence that l integrins are required for normal hair follicle development came in a recent study of mice whose keratinocytes don't express the l integrin gene. These mice had profound hair follicle abnormalities and reduced cell division in the hair follicle epithelium4.In embryonic human follicles, l integrin is expressed almost universally by epithelial cells early on, but as development proceeds this expression becomes progressively restricted to the 'bulge' region5. A bulge region has been delineated in mature human follicles with an antibody that recognizes cytokeratin 15 but, in contrast to mice, this labeled region represents a significant segment of the follicle ORS.6 A more-direct method of identifying stem cells involves isolating single cells, and comparing their ability to produce colonies and be serially maintained in culture. When human hair follicles were sectioned and the clonogenic potential of cells from each level was tested7, the region of the human follicle that best corresponded to the mouse 'bulge' was found to have some cells with colony-forming ability, but many more colony-forming cells were found further down the outer root sheath around and below the mid-point of the follicle.These observations indicate that human stem cells are widely distributed along the length of the follicle outer root sheath, and explain how surgeons can repeatedly remove split-thickness grafts from the same donor site. They also have relevance for treatments that rely directly on the clonogenic potential of cells. For example, a small piece of a patient's skin can be cultured and rapidly expanded to produce sheets of epidermis suitable for grafting. Hair follicle outer root sheath has already been tested as a specific source of epidermis and, if the stem cell location is not too restricted, then culturing sheets of cells from almost any region of the outer root sheath should provide the stem cells necessary for long-term graft survival in these, or more sophisticated, tissue-engineered skin equivalents.For years, researchers have believed that several types of skin cancers are derived from hair follicles, based on observations of molecular markers common to both. Concern about follicle stem cell location has overlapped with a debate about the precise site of origin of particular tumors. More thought-provoking studies link tumor formation to inappropriate activity of molecules that are expressed as part of normal epithelial-mesenchymal signaling. This controls follicle embryogenesis, hair growth and the unique cycling behavior of adult follicles, and the molecular pathways involved are common regulators in many developmental systems.Others have previously demonstrated that -catenin, an element of the Lef 1/Wnt singaling pathway, produces skin tumors when inappropriately expressed in mice8. The equivalent human tumors are derived from matrix epithelium of the lower follicle9. The sonic hedgehog (Shh) pathway is also important for follicle development and growth and pathogenesis of basal cell carcinomas (BCCs), common skin tumors, is thought to involve constitutive activation of the Shh pathway. Gli transcription factors are possible downstream effectors for this transformation, and transgenic mice overexpressing Gli2 have recently been shown to produce BCCs (ref. 10). Likewise, Gli1 has been located in BCCs the ORS and mesenchyme immediately surrounding the bulge in human follicles11.Two messages emerge from these and related studies: Different regions of the follicle epithelium can produce tumors, and in normal and pathological skin, epithelial−mesenchymal interactions are involved. Taylor et al. discussed whether skin has its own distinct stem cell population1. As the authors used newborn skin, which is still growing, it is not certain that cells flow from the hair follicle to the epidermis in undamaged adult skin, or if this is connected with follicle cycling. Perhaps, as the authors suggest, the follicle is the ultimate source of stem cells, the epidermis-containing follicle-derived progenitors. Alternatively, it is possible that newborn skin is 'seeded' with migrating follicle-derived cells while it is still expanding.Nonetheless, recent 'seismic' discoveries in developmental biology demonstrating the ability to completely reprogram adult stem cells, such as the ability to convert nerve cells to blood cells, has resonance for all stem cell biology12. Real estate agents selling a house say that only three things are important: location, location and location. These reprogamming experiments are a reminder that the same is true in stem cell biology - the environment, or niche, is an essential factor13.A classic experiment that laid the foundations for much current hair follicle biology showed that adult skin epidermis will form a new follicle and grow hair under the inductive influence of the principal mesenchymal follicular component, the dermal papilla. Given that the function of the epidermis can be changed to become follicle epithelium, it may be better not to become too entangled in definitions. It may be preferable to develop the important avenues of research and practical possibilities that Taylor et al. have demonstrated, and to keep delving into the hair follicle; it is likely to hold many more surprises.


Cancer stem cell
Cancer stem cells (CSCs) are a sub-population of cancer cells (found within tumors or hematological cancers) that possess characteristics normally associated with stem cells. These cells are believed to be tumorigenic (tumor-forming), in contrast to the bulk of cancer cells, which are thought to be non-tumorigenic. CSCs have stem cell properties such as self-renewal and the ability to differentiate into multiple cell types. A theory suggests such cells persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumours. Development of specific therapies targeted at cancer stem cells holds hope for improvement of survival and quality of life of cancer patients, especially for sufferers of metastatic disease.
Existing cancer treatments were mostly developed on animal models, where therapies able to promote tumor shrinkage were deemed effective. However, animals could not provide a complete model of human disease. In particular, in mice, whose life spans do not exceed two years, tumor relapse is exceptionally difficult to study.
The efficacy of cancer treatments are, in the initial stages of testing, often measured by the amount of tumour mass they kill off. As cancer stem cells would form a very small proportion of the tumour, this may not necessarily select for drugs that act specifically on the stem cells. The theory suggests that conventional chemotherapies kill differentiated or differentiating cells, which form the bulk of the tumor but are unable to generate new cells. A population of cancer stem cells, which gave rise to it, could remain untouched and cause a relapse of the disease.


Evidence for cancer stem cells
Opponents of the paradigm do not deny the existence of cancer stem cells as such. Cancer cells must be capable of continuous proliferation and self-renewal in order to retain the many mutations required for carcinogenesis, and to sustain the growth of a tumor since differentiated cells cannot divide indefinitely (constrained by the Hayflick Limit). However, it is debated whether such cells represent a minority. If most cells of the tumor are endowed with stem cell properties there is no incentive to focusing on a specific subpopulation. There is also debate on the cell of origin of these cancer stem cells - whether they originate from stem cells that have lost the ability to regulate proliferation, or from more differentiated population of progenitor cells that have acquired abilities to self-renew (which is related to the issue of stem cell plasticity).
The first conclusive evidence for cancer stem cells was published in 1997 in Nature Medicine. Bonnet and Dick isolated a subpopulation of leukaemic cells that express a specific surface marker CD34, but lacks the CD38 marker. The authors established that the CD34+/CD38- subpopulation is capable of initiating tumors in NOD/SCID mice that is histologically similar to the donor. (Matsui, 2004)
In cancer research experiments, tumor cells are sometimes injected into an experimental animal to establish a tumor. Disease progression is then followed in time and novel drugs can be tested for their ability to inhibit it. However, efficient tumor formation requires thousands or tens of thousands of cells to be introduced. Classically, this has been explained by poor methodology (i.e. the tumor cells lose their viability during transfer) or the critical importance of the microenvironment, the particular biochemical surroundings of the injected cells. Supporters of the cancer stem cell paradigm argue that only a small fraction of the injected cells, the cancer stem cells, have the potential to generate a tumor. In human acute myeloid leukemia the frequency of these cells is less than 1 in 10,000.[1]
Further evidence comes from histology, the study of tissue structure of tumors. Many tumors are very heterogeneous and contain multiple cell types native to the host organ. Heterogeneity is commonly retained by tumor metastases. This implies that the cell that produced them had the capacity to generate multiple cell types. In other words, it possessed multidifferentiative potential, a classical hallmark of stem cells.[1]

Importance of stem cells
Not only is finding the source of cancer cells necessary for successful treatments, but if current treatments of cancer do not properly destroy enough cancer stem cells, the tumor will reappear. Including the possibility that the treatment of for instance, chemotherapy, will leave only chemotherapy-resistant cancer stem cells, then the ensuing tumor will most likely also be resistant to chemotherapy. If the cancer tumor is detected early enough, enough of the tumor can be killed off and marginalized with traditional treatment. But as the tumor size increases, it becomes more and more difficult to remove the tumor without conferring resistance and leaving enough behind for the tumor to reappear.
Some treatments with chemotherapy, such as paclitaxel in ovarian cancer (a cancer usually discovered in late stages), may actually serve to promote certain cancer growth (55-75% relapse <2 title="CD44" href="http://en.wikipedia.org/wiki/CD44">CD44-positive, a trait which has been associated with increased survival time in some ovarian cancers), and allowing the cells which are unaffected by paclitaxel (CD44-negative) to regrow, even after a reduction in over a third of the total tumor size. There are studies, though, which show how paclitaxel can be used in combination with other ligands to affect the CD44-positive cells. While paclitaxel alone, as of late, does not cure the cancer, it is effective at extending the survival time of the patients.

Implications for cancer treatment
The existence of cancer stem cells have several implications in terms of future cancer treatment and therapies. These include disease identification, selective drug targets, prevention of metastasis, and development of new strategies in fighting cancer.
Normal somatic stem cells are naturally resistant to chemotherapeutic agents - they have various pumps (such as MDR) that pump out drugs, DNA repair proteins and they also have a slow rate of cell turnover (chemotherapeutic agents naturally target rapidly replicating cells). Cancer stem cells, being the mutated counterparts of normal stem cells, may also have similar functions which allows them to survive therapy. These surviving cancer stem cells then repopulates the tumour, causing relapse. By selectively targeting cancer stem cells, it would be possible to treat patients with aggressive, non-resectable tumours, as well as preventing the tumour from metastasizing. The hypothesis implies that if the cancer stem cells are eliminated, the cancer would simply regress due to differentiation and cell death.
There has also been a lot of research into finding specific markers that may distinguish cancer stem cells from the bulk of the tumour (as well as from normal stem cells), with some success. Proteomic and genomic signatures of tumours are also being investigated. Success in these area would enable faster identification of tumour subtypes as well as personalized medicine in cancer treatments by using the right combination of drugs and/or treatments to efficiently eliminate the tumour.\




Stem cell treatment of Multiple Sclerosis
Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (brain and spinal cord). The disease process results in inflammation and damage to myelin (the insulating tissue for nerve fibers) and other cells within the nervous system.
Because myelin aids the conduction of nerve signals, damage to myelin results in impaired nerve signaling and may impair normal sensation, movement, and thinking. This damage occurs in patches that appear as distinct lesions on magnetic resonance imaging (MRI). The patches cause different symptoms, depending on their location within the nervous system.

Multiple Sclerosis treatment
The stem cells are first collected from a patient’s bone marrow, extracted from the hipbone (iliac crest) then implanted back into the body days later. Prior to re-implantation of the cells, the bone marrow is processed in one of our labs, where the quantity and quality of the stem cells is also checked.
These re-injected stem cells have the potential to transform into multiple types of cells and are capable of regenerating damaged tissue. Our innovative stem cell treatments use the self-healing potential of each patient’s own body to stimulate regeneration or repair.
Currently there is no cure for MS. There are treatments available that may slow its progression and alleviate associated symptoms. Stem cell therapy is among these treatment options.


Stem cells in the treatment of ischemic diseases.
Ischemia causes oxygen deprivation, cell injury and related organ dysfunction. Although ischemic injury may be local, it involves many biochemical changes in different cell types. The ability of stem cells to differentiate into different cell lineages provides the possibility of their use in treating a variety of diseases requiring tissue repair or reconstitution, such as stroke, ischemic retinopathy, myocardial infarction, ischemic disorders of the liver, ischemic renal failure, and ischemic limb dysfunction. Several cell types including embryonic stem cells, various progenitor and stem cells of hematopoietic or mesenchymal origin have been used in attempts to reconstitute injured tissue. Xenologous or autologous stem cells may be administered either through the peripheral vascular system or directly by regional injection. The stem cells are then guided to the infarct site by homing signals. Either by cell differentiation or paracrine effects, stem cells or progenitor cells participate in the reconstruction of a favorable microenvironment resulting in neovascularization and tissue regeneration that eventually improve the physiological function of organs with ischemic damage


Severe combined immunodeficiency
Severe combined immunodeficiency (SCID), or Boy in the Bubble Syndrome, is a genetic disorder in which both "arms" (B cells and T cells) of the adaptive immune system are crippled, due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency. It is also known as the "bubble boy" disease because its victims are extremely vulnerable to infectious diseases. The most famous case is the boy David Vetter.
Chronic diarrhea, ear infections, recurrent Pneumocystis jirovecii pneumonia, and profuse oral candidiasis commonly occur. These babies, if untreated, usually die within 1 year due to severe, recurrent infections. However, treatment options are much improved since David Vetter

Treatment
The most common treatment for SCID is bone marrow transplantation, which has been successful using either a matched donor (a sibling is generally best)or a half-matched donor, who would be either parent. The half-matched type of transplant is called haplo-identical and was perfected by Memorial Sloan Kettering Cancer Center in New York and also Duke University Medical Center which currently does the highest number of these transplants of any center in the world. David Vetter, the original "bubble boy", had one of the first transplantations but eventually died because of an unscreened virus, Epstein-Barr (tests were not available at the time), in his newly transplanted bone marrow from his sister. Today, transplants done in the first three months of life have a high success rate. Physicians have also had some success with in utero transplants done before the child is born and also by using cord blood which is rich in stem cells.
More recently gene therapy has been attempted as an alternative to the bone marrow transplant. Transduction of the missing gene to hematopoietic stem cells using viral vectors is being tested in ADA SCID and X-linked SCID. The first gene therapy trials were performed in 1990, with peripheral T cells. In 2000, the first gene therapy "success" resulted in SCID patients with a functional immune system. These trials were stopped when it was discovered that two of ten patients in one trial had developed leukemia resulting from the insertion of the gene-carrying retrovirus near an oncogene. In 2007, four of the ten patients have developed leukemias. Work is now focusing on correcting the gene without triggering an oncogene. No leukemia cases have yet been seen in trials of ADA-SCID, which does not involve the gamma c gene that may be oncogenic when expressed by a retrovirus.
Trial treatments of SCID have been gene therapy's only success; since 1999, gene therapy has restored the immune systems of at least 17 children with two forms (ADA-SCID and X-SCID) of the disorder.

HIV / AIDS Treatment Directions
The idea is to replace the gene that is vulnerable to attack by HIV with a synthetically engineered piece of DNA designed to seek out and destroy the virus. The DNA fragment, known as a ribozyme, is tailored specifically to bind to HIV and cut it in half, rendering it harmless.

Patients are first given a growth factor that stimulates bone marrow stem cells to enter the bloodstream. Then blood is drawn, and the patients' own stem cells are isolated from the blood. Next, the gene is inserted into the cells by a modified, harmless virus related to HIV. Then the stem cells, armed with their new weapon, are returned to the bloodstream, where they begin making all the different types of blood cells, each of which will inherit the new anti-HIV gene. The method can protect about 10 percent of the patients' stem cells, but as HIV slowly kills the vulnerable cells and protected cells continue to replicate, the percentage will increase. To speed the process, six months after receiving the infusion of modified cells, patients will stop taking their anti-viral medications for four weeks to give the virus a chance to kill off some unprotected blood cells, putting pressure on the protected cells to replicate faster to replace them. This is repeated again after 12 weeks, when the patients go off their medication for at least eight weeks and potentially longer, depending on how well the strategy works to reduce the level of HIV in the patients' blood. The trial will be finished in about a year and a half.


Diseases of Bone and Cartilage
Stem cells, once appropriately differentiated, could
correct many diseases and degenerative conditions in which bone or cartilage cells are
deficient in numbers or defective in function. This holds promise for treatment of genetic
disorders such as osteogenesis imperfecta and chondrodysplasias. Similarly, cells could
be cultivated and introduced into damaged areas of joint cartilage in cases of osteoarthritis
or into large gaps in bone from fractures or surgery.



Erectile Dysfunction
Erectile Dysfunction, sometimes called ‘impotence’, is the repeated inability to get or keep an erection firm enough for sexual intercourse. The word ‘impotence’ may also be used to describe other problems that interfere with sexual intercourse and reproduction, such as lack of sexual desire and problems with ejaculation or orgasm. Using the term erectile dysfunction makes it clear that those other problems are not involved.
Damage to nerves, arteries, smooth muscles, and fibrous tissues, often as a result of a disease, is the most common cause of erectile penile dysfunction. Diseases such as diabetes, kidney disease, chronic alcoholism, multiple sclerosis, atherosclerosis, vascular disease, and neurologic disease, account for about 70 percent of erectile dysfunction cases. Between 35 and 50 percent of men with diabetes experience erectile dysfunction.





Reprogramming of stem cells

By this Concept One can make stem cells from any cell of Body
In May 2006, Japanese researchers became the first to report the reprogramming of adult mouse skin cells, helping them regain the pluripotency seen in embryonic stem cells. The science seemed relatively simple: they added genes for four transcription factors - which express proteins involved in gene activity - to the growing cells and so-called induced pluripotent stem (iPS) cells were made.
Since then, several groups have published reports of reprogramming mature human skin cells to a pluripotent state.
These are exciting advances, particularly as the creation of iPS cells does not require the use of embryos - the limited supply of which is a key barrier to current stem cell research. However, a number of key questions about iPS cells remain. To date, research in this area has relied on viral vectors for getting the genes required for reprogramming into cells. Researchers are still to establish whether the integration of the viral genes into the cells' genome and/or some other genetic effects of the process plays some part in the reprogramming. It is also unclear which genes are required for the actual reprogramming, and which are required to trigger cell proliferation.
The major question though is whether iPS cells and embryonic stem cells are equivalent. To find out, researchers are comparing iPS cells and embryonic stem cells in a number of ways, including by looking at proteins on the surface of the cells that indicate pluripotency, and at the expression of genes within the cells
There were three papers published this week that showed how to reprogram somatic cells so they could act like embryonic stem cells. The trick is to introduce genes for four different transcription factors into the somatic cells (e.g., skin cells). When the four transcription factors (Oct4, Sox2, c-Myc, and Klf4) are made they turn on genes in the somatic cell that cause it to reprogram and become competent to differentiate into any other type of cell, including germ cells.

Controversy surrounding human embryonic stem cell research
There exists a widespread controversy over human embryonic stem cell research that emanates from the techniques used in the creation and usage of stem cells. Human embryonic stem cell research is controversial because, with the present state of technology, starting a stem cell line requires the destruction of a human embryo and/or therapeutic cloning. However, recently, it has been shown in principle that adult stem cell lines can be manipulated to generate embryonic-like stem cell lines using a single-cell biopsy similar to that used in preimplantation genetic diagnosis that may allow stem cell creation without embryonic destruction. It is not the entire field of stem cell research, but the specific field of human embryonic stem cell research that is at the centre of an ethical debate.
Opponents of the research argue that embryonic stem cell technologies are a slippery slope to reproductive cloning and can fundamentally devalue human life. Those in the pro-life movement argue that a human embryo is a human life and is therefore entitled to protection.
Contrarily, supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It is also noted that excess embryos created for in vitro fertilization could be donated with consent and used for the research.
The ensuing debate has prompted authorities around the world to seek regulatory frameworks and highlighted the fact that stem cell research represents a social and ethical challenge.

Ethical, legal and social issues for Stem Cells Research
There are several types of issues to consider as we think about stem cell research.
Ethical issues are those that ask us to consider the potential moral outcomes of stem cell technologies.
Legal issues require researchers and the public to help policymakers decide whether and how stem cell technologies should be regulated by the government.
Social issues involve the impact of stem cell technologies on society as a whole.
Some questions to ponder.
The questions raised here have no clear right or wrong answer. Instead, your response will depend on your own set of values, as well as the opinions of those around you.
How far should researchers take stem cell technologies? Just because we can do something, should we? Why or why not?
Should the government provide funding for embryonic stem cell research? Why or why not?
Should there be laws to regulate stem cell research? If so, what would they look like? For example, how would you regulate research using different types of stem cells, such as embryonic, fetal or adult stem cells? What about embryonic stem cells created using cloning technologies?
Do embryonic stem cells represent a human life? This is an ongoing debate that brings up the question of when life begins. Should the embryo or fetus have any rights in the matter? Who has the authority to decide?
Should frozen embryos created through in vitro fertilization be used to create stem cells? Why or why not?


Stem cell funding & policy debate in the US
1993 - As per the National Institutes of Health Revitalization Act, Congress and President Bill Clinton give the NIH direct authority to fund human embryo research for the first time.
1995 - The U.S. Congress enacts into law an appropriations bill attached to which is the Dickey Amendment which prohibited federally appropriated funds to be used for research where human embryos would be either created or destroyed. This predates the creation of the first human embryonic stem cell lines.
1999 - After the creation of the first human embryonic stem cell lines in 1998 by James Thomson of the University of Wisconsin, Harriet Rabb, the top lawyer at the Department of Health and Human Services, releases a legal opinion that would set the course for Clinton Administration policy. Federal funds, obviously, could not be used to derive stem cell lines (because derivation involves embryo destruction). However, she concludes that because human embryonic stem cells "are not a human embryo within the statutory definition," the Dickey-Wicker Amendment does not apply to them. The NIH was therefore free to give federal funding to experiments involving the cells themselves. President Clinton strongly endorses the new guidelines, noting that human embryonic stem cell research promised "potentially staggering benefits." And with the guidelines in place, the NIH begins accepting grant proposals from scientists.
02 November, 2004 - California voters approve Proposition 71, which provides $3 billion in state funds over ten years to human embryonic stem cell research.
2001-2006 - U.S. President George W. Bush signs an executive order which restricts federally-funded stem cell research on embryonic stem cells to the already derived cell lines. He supports federal funding for embryonic stem cell research on the already existing lines of approximately $100 million and $250 million for research on adult and animal stem cells.
5 May, 2006 - Senator Rick Santorum introduces bill number S. 2754, or the Alternative Pluripotent Stem Cell Therapies Enhancement Act, into the U.S. Senate.
18 July, 2006 - The U.S. Senate passes the Stem Cell Research Enhancement Act H.R. 810 and votes down Senator Santorum's S. 2754.
19 July, 2006 - President George W. Bush vetoes H.R. 810 (Stem Cell Research Enhancement Act), a bill that would have reversed the Gingrich-era appropriations amendment which made it illegal for federal money to be used for research where stem cells are derived from the destruction of an embryo.
07 November, 2006 - The people of the U.S. state of Missouri passed Amendment 2, which allows usage of any stem cell research and therapy allowed under federal law, but prohibits human reproductive cloning.
16 February, 2007 – The California Institute for Regenerative Medicine became the biggest financial backer of human embryonic stem cell research in the United States when they awarded nearly $45 million in research grants.


Key stem cell research events
1908 - The term "stem cell" was proposed for scientific use by the Russian histologist Alexander Maksimov (1874-1928) at congress of hematologic society in Berlin. It postulated existence of haematopoietic stem cells.
1960s - Joseph Altman and Gopal Das present scientific evidence of adult neurogenesis, ongoing stem cell activity in the brain; their reports contradict Cajal's "no new neurons" dogma and are largely ignored.
1963 - McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow.
1968 - Bone marrow transplant between two siblings successfully treats SCID.
1978 - Haematopoietic stem cells are discovered in human cord blood.
1981 - Mouse embryonic stem cells are derived from the inner cell mass by scientists Martin Evans, Matthew Kaufman, and Gail R. Martin. Gail Martin is attributed for coining the term "Embryonic Stem Cell".
1992 - Neural stem cells are cultured in vitro as neurospheres.
1997 - Leukemia is shown to originate from a haematopoietic stem cell, the first direct evidence for cancer stem cells.
1998 - James Thomson and coworkers derive the first human embryonic stem cell line at the University of Wisconsin-Madison.
2000s - Several reports of adult stem cell plasticity are published.
2001 - Scientists at Advanced Cell Technology clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.
2003 - Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth.
2004-2005 - Korean researcher Hwang Woo-Suk claims to have created several human embryonic stem cell lines from unfertilised human oocytes. The lines were later shown to be fabricated.
2005 - Researchers at Kingston University in England claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical cord blood. The group claims these cells are able to differentiate into more types of tissue than adult stem cells.
August 2006 - Rat Induced pluripotent stem cells: the journal Cell publishes Kazutoshi Takahashi and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors".
October 2006 - Scientists at Newcastle University in England create the first ever artificial liver cells using umbilical cord blood stem cells.
January 2007 - Scientists at Wake Forest University led by Dr. Anthony Atala and Harvard University report discovery of a new type of stem cell in amniotic fluid.[5] This may potentially provide an alternative to embryonic stem cells for use in research and therapy.
June 2007 - Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.[37] In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer[38]
October 2007 - Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.
November 2007 - Human Induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors", and in Science by Junying Yu, et al., from the research group of James Thomson, "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells": pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of tumorigenesis due to c-myc and retroviral gene transfer remains to be determined.
January 2008 - Human embryonic stem cell lines were generated without destruction of the embryo
January 2008 - Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts
February 2008 - Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach: these iPS cells seem to be more similar to embryonic stem cells than the previous developed iPS cells and not tumorigenic, moreover genes that are required for iPS cells do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques.
March 2008-The first published study of successful cartilage regeneration in the human knee using autologous adult mesenchymal stem cells is published by Clinicians from Regenerative Sciences.