Federal money may, however, be used to research lines that were derived using private or state sources of funding. While funding restrictions and political debates may have slowed the course of stem cell research in the United States, 10 the field continues to evolve.
This is evidenced by the large number of studies published each year in scientific journals on a wide range of potential uses across a variety of therapeutic areas. A report from the Pharmaceutical Research and Manufacturers of America lists 69 cell therapies as having clinical trials under review with the FDA, including 15 in phase 3 trials.
The therapeutic categories represented in these trials include cardiovascular disease, skin diseases, cancer and related conditions, digestive disorders, transplantation, genetic disorders, musculoskeletal disorders, and eye conditions, among others.
Still, the earliest stem cell therapies are likely years away. To date, the only stem cell—based treatment approved by the FDA for use in this country is for bone marrow transplantation. Research on stem cells began in the late 19th century in Europe. German biologist Ernst Haeckel coined the term stem cell to describe the fertilized egg that becomes an organism.
In the U. Stevens, a cancer researcher based in Bar Harbor, Maine, found large tumors in the scrotums of mice that contained mixtures of differentiated and undifferentiated cells, including hair, bone, intestinal, and blood tissue. Stevens and his team concluded that the cells were pluripotent, meaning they could differentiate into any cell found in a fully grown animal.
Stem cell scientists are using that carefully documented research today. In , Robert A. Good, MD, PhD, at the University of Minnesota, performed the first successful bone marrow transplant on a child suffering from an immune deficiency.
Scientists subsequently discovered how to derive ESCs from mouse embryos and in developed a method to take stem cells from a human embryo and grow them in a laboratory. Many degenerative and currently untreatable diseases in humans arise from the loss or malfunction of specific cell types in the body.
Stem cells have two important and unique characteristics: First, they are unspecialized and capable of renewing themselves through cell division. Stem cells can theoretically divide without limit to replenish other cells that have been damaged. Second, under certain controlled conditions, stem cells can be induced to become tissue- or organ-specific cells with special functions.
They can then be used to treat diseases affecting those specific organs and tissues. While bone marrow and gut stem cells divide continuously throughout life, stem cells in the pancreas and heart divide only under appropriate conditions. There are two main types of stem cells: 1 embryonic stem cells ESCs , found in the embryo at very early stages of development; and 2 somatic or adult stem cells ASCs , found in specific tissues throughout the body after development.
The advantage of embryonic stem cells is that they are pluripotent—they can develop into any of the more than cell types found in the body, providing the potential for a broad range of therapeutic applications. Adult stem cells, on the other hand, are thought to be limited to differentiating into different cell types of their tissue of origin.
A significant advantage of adult stem cells is that they offer the potential for autologous stem cell donation. In autologous transplants, recipients receive their own stem cells, reducing the risk of immune rejection and complications. Additionally, ASCs are relatively free of the ethical issues associated with embryonic stem cells and have become widely used in research. Representing a relatively new area of research, induced pluripotent stem cells iPSCs are adult stem cells that have been genetically reprogrammed back to an embryonic stem cell—like state.
The reprogrammed cells function similarly to ESCs, with the ability to differentiate into any cell of the body and to create an unlimited source of cells. So iPSCs have significant implications for disease research and drug development. Pioneered by Japanese researchers in , iPSC technology involves forcing an adult cell, such as a skin, liver, or stomach cell, to express proteins that are essential to the embryonic stem cell identity.
Like adult cells, these unlimited supplies of autologous cells could be used to generate transplants without the risk of immune rejection. In , researchers at the Spanish National Cancer Research Centre in Madrid successfully reprogrammed adult cells in mice, creating stem cells that can grow into any tissue in the body. Prior to this study, iPSCs had never been grown outside Petri dishes in laboratories.
The Riken Center for Developmental Biology will use the cells to attempt to treat age-related macular degeneration, a common cause of blindness in older people.
Although most of the media attention around stem cells has focused on regenerative medicine and cell therapy, researchers are finding that iPSCs, in particular, hold significant promise as tools for disease modeling. In addition to using iPSC technology, it is also possible to derive patient-specific stem cell lines using an approach called somatic cell nuclear transfer SCNT. This process involves adding the nuclei of adult skin cells to unfertilized donor oocytes. The insulin-producing cells have two sets of chromosomes the normal number in humans and could potentially be used to develop personalized cell therapies.
The development of iPSCs and related technologies may help address the ethical concerns and open up new possibilities for studying and treating disease, but there are still barriers to overcome.
One major obstacle is the tendency of iPSCs to form tumors in vivo. Using viruses to genomically alter the cells can trigger the expression of cancer-causing genes, or oncogenes. Much more research is needed to understand the full nature and potential of stem cells as future medical therapies. It is not known, for example, how many kinds of adult stem cells exist or how they evolve and are maintained.
Some of the challenges are technical, Dr. Owens explains. For instance, generating large enough numbers of a cell type to provide the amounts needed for treatment is difficult. Some adult stem cells have a very limited ability to divide, making it difficult to multiply them in large numbers. Embryonic stem cells grow more quickly and easily in the laboratory. This is an important distinction because stem cell replacement therapies require large numbers of cells.
Also, says Dr. Or, you might have immunosuppression with the individual who received the cells, and then there are additional complications involved with that. Such safety issues need to be addressed before any new stem cell—based therapy can advance to clinical trials with real patients. According to Dr. Owens, the preclinical testing stage typically takes about five years. This would include assessment of toxicity, tumorigenicity, and immunogenicity of the cells in treating animal models for disease.
Owens says. Collaboration is essential. Ultimately, stem cells have huge therapeutic potential, and numerous studies are in progress at academic institutions and biotechnology companies around the country. Studies at the NIH span multiple disciplines, notes Dr.
Figure 1 shows the recent history of NIH funding for stem cell research. He describes one area of considerable interest as the promotion of regeneration in the brain based on endogenous stem cells. Until recently, it was believed that adult brain cells could not be replaced. However, the discovery of neurogenesis in bird brains in the s led to startling evidence of neural stem cells in the human brain, raising new possibilities for treating neurodegenerative disorders and spinal cord injuries.
They could probably play different roles in different species, but just the fundamental properties themselves are very interesting. A second ACT trial is testing the safety of hESC-derived retinal cells to treat age-related macular degeneration patients.
In April , scientists at the University of Washington reported that they had successfully regenerated damaged heart muscles in monkeys using heart cells created from hESCs. The research, published in the journal Nature , was the first to show that hESCs can fully integrate into normal heart tissue.
In May , Asterias Biotherapeutics, a California-based biotechnology company focused on regenerative medicine, announced the results of a phase 1 clinical trial assessing the safety of its product AST-OPC1 in patients with spinal cord injuries. Results show that all five subjects have had no serious adverse events associated with the administration of the cells, with the AST-OPC1 itself, or with the immunosuppressive regimen. The FDA itself has a team of scientists studying the potential of mesenchymal stem cells MSCs , adult stem cells traditionally found in the bone marrow.
Multipotent stem cells, MSCs differentiate to form cartilage, bone, and fat and could be used to repair, replace, restore, or regenerate cells, including those needed for heart and bone repair. However, the FDA cautions that the information provided on that site is supplied by the product sponsors and is not reviewed or confirmed by the agency. If we get a better handle on the disorders themselves, then that will also help us generate new therapeutic targets.
More than 26, patients are treated with blood stem cells in Europe each year. Since the s, skin stem cells have been used to grow skin grafts for patients with severe burns on very large areas of the body. Only a few clinical centres are able to carry out this treatment and it is usually reserved for patients with life-threatening burns.
A new stem-cell-based treatment to repair damage to the cornea the surface of the eye after an injury like a chemical burn, has received conditional marketing approval in Europe. Stem cell therapy using tissue stem cells has been in routine use since the s! Skin stem cells have been used since the s to grow sheets of new skin in the lab for severe burn patients. However, the new skin has no hair follicles, sweat glands or sebaceous oil glands, so the technique is far from perfect and further research is needed to improve it.
Currently, the technique is mainly used to save the lives of patients who have third degree burns over very large areas of their bodies and is only carried out in a few clinical centres. Cord blood stem cells can be harvested from the umbilical cord of a baby after birth. Treatment of adults has been more challenging, due to the low cell number obtained from one umbilical cord. As such adult treatment requires a double unit cord blood transplantation i. And although one advantage of cord blood transplants is that they appear to be less likely to be rejected by the immune system than conventional bone marrow transplants, cord blood must still be matched to the patient to be successful.
And even then an increased immune response in adult recipients might cause problems. So far, only blood diseases can be treated with cord blood stem cells.
Although some studies have suggested cord blood may contain stem cells that can produce other types of specialised cells not related to the blood, none of this research has been confirmed. Mesenchymal stem cells MSCs are found in the bone marrow and are responsible for bone and cartilage repair. On top of that, they can also produce fat cells.
Early research suggesting that MSCs could differentiate into many other cell types and that they could also be obtained from a wide variety of tissues other than bone marrow have not been confirmed. There is still considerable scientific debate surrounding the exact nature of the cells which are also termed Mesenchymal stem cells obtained from these other tissues.
As of now, no treatments using mesenchymal stem cells are proven to be effective. There are, however, some clinical trials investigating the safety and effectiveness of MSC treatments for repairing bone or cartilage.
Other trials are investigating whether MSCs might help repair blood vessel damage linked to heart attacks or diseases such as critical limb ischaemia, but it is not yet clear whether these treatments will be effective. Several other features of MSCs, such as their potential effect on immune responses in the body to reduce inflammation to help treat transplant rejection or autoimmune diseases are still under thorough investigation.
It will take numerous studies to evaluate their therapeutic value in the future. Clinical studies in patients have shown that tissue stem cells taken from an area of the eye called the limbus can be used to repair damage to the cornea — the transparent layer at the front of the eye. However, this can only help patients who have some undamaged limbal stem cells remaining in one of their eyes.
The treatment has been shown to be safe and effective in clinical trials and has now been approved by regulatory authorities for widespread use in Europe. Limbal stem cells are one of only three stem cell therapies treatments utilising blood stem cells and skin stem cells being the other two that are available through healthcare providers in Europe. Recently, human ESCs embryonic stem cells that meet the strict quality requirements for use in patients have been produced.
One example is a clinical trial carried out by The London Project to Cure Blindness , using ESCs to produce a particular type of eye cell for treatment of patients with age-related macular degeneration AMD.
Model replicates features of complex disease, provides platform for screening existing drugs. Using a stem-cell-derived model, researchers have identified two drug candidates that may slow dry age-related macular degeneration AMD , a leading cause of blindness for which no treatment exists. Chiang M. The causes of AMD involve a yet-to-be-understood combination of genetic factors, aging, and behavior-related risk factors such as smoking and diet.
The researchers used the model to screen drugs to see if they may slow or halt disease progression. Two drugs prevented the model from developing key phenotypes: the accumulation of drusen, lipid-rich deposits in the retina, and the atrophy, or shrinkage, of retinal pigment epithelium RPE cells.
Loss of RPE leads to the death of photoreceptors and in turn, to loss of vision. Led by Kapil Bharti, Ph. Previous genetic studies had shown that some AMD patients have variants in genes responsible for regulating the alternate complement pathway, a key part of the immune system.
However, it was unclear how the genetic variants led to disease. One hypothesis was that patients with such variants lacked the ability to regulate the alternate complement pathway once it had become activated, resulting in the formation of anaphylatoxins, a type of protein that mediates inflammation, among other biological functions.
To test this hypothesis, the researchers exposed 10 iPSC-derived RPE cell lines involving different genetic variants to anaphylatoxins from human serum.
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