Having the ability to replace the lost and damaged cells and the plasticity to develop into other types of cells, stem cells seem to provide unprecedented opportunities for treating a range of diseases, including those currently considered incurable. However, despite the spur of stem cell research during the past two decades, its clinical application remains challenging.
What are stem cells?
Most cells in the human body are specialized to complete a certain function: muscle cells contract, neural cells transmit the signals, and glands produce the hormones. The more specified a cell, the lower its ability to replicate.
However, a small number of cells remain relatively unspecialized, and they retain their ability to renew themselves and may differentiate into other types of cells. To some extent, these cells resemble the cells in a human embryo, which give rise to various tissues and organs.
The cells that can renew themselves and develop into other types of cells are called stem cells.
What are the sources of stem cells?
Stem cells may be collected from the living tissues, expanded in the amount if needed, or produced in the laboratory. There are three different types of stem cells:
Embryonic stem cells are the most versatile stem cells, i.e., they can develop into any other type of cell and are thus called pluripotent. They are derived from an embryo aged up to five days. The use of embryonic stem cells is intensively disputed due to ethical and moral issues.
Perinatal stem cells can be easily collected from the amniotic fluid that surrounds the fetus as well as from the umbilical cord after the baby is born. This collection does not harm the fetus or the baby. However, perinatal stem cells have somewhat lower differentiation potential compared to embryonic stem cells.
Adult stem cells, such as hematopoietic stem cells or mesenchymal stem cells, serve as a reservoir for the growth and replacement of cells that are lost each day. They can be retrieved from a person’s bone marrow or fat. Their differentiation potential is even lower compared to perinatal stem cells, but they can still develop into several types of cells.
To overcome ethical issues while preserving pluripotency, techniques to artificially generate stem cells have been developed. Mature cells can be reprogrammed into pluripotent stem cells by genetic manipulation. Such cells are called induced pluripotent stem cells.
Shinya Yamanaka and John Gurdon received the Nobel Prize for the discovery of this method in 2012.
How do stem cells work?
Transplanted stem cells provide therapeutic benefits not only by replacing the damaged tissues but also by modulating the immune response, releasing substances that provide support for surrounding tissues, and promoting the growth of the blood vessels.
What types of stem cell treatments are currently available?
Despite the tremendous scientific interest in stem cells, a limited number of stem cell therapies are currently approved for routine use.
One of the most widely applied stem cell therapies is hematopoietic stem cell transplantation, which has already been used to treat certain blood cancers and immune system diseases for decades.
Stem cells can be collected from the bone marrow or blood of a patient (autologous transplantation) or a matched donor (allogeneic transplantation). Also, several approved umbilical cord blood products are available in the US for hematopoietic stem cell transplantation.
Mesenchymal stem cell preparation has been approved for the treatment of graft versus host disease, a life-threatening complication after allogeneic bone marrow transplantation where transplanted cells attack the healthy cells of the patient.
Commercially available mesenchymal stem cells preparation taken from fat tissue has been authorized for use in Crohn’s disease (an inflammatory large intestine disease) complicated by perianal fistula (an opening leading from the intestine to the skin surface).
Several stem cell and more mature cell preparations have been approved and marketed in Japan, Australia, India, and Iran for the treatment of various skin, cartilage, and bone defects.
What are the potential stem cell applications in the future?
The frontline areas for stem cell research are neurological disorders (stroke, multiple sclerosis, spinal cord injury, Alzheimer’s, Parkinson’s, and Huntington’s diseases), degenerative vision disorders, osteoarthritis, cardiovascular diseases (myocardial infarction and heart failure), chronic liver disease, periodontal tissue regeneration, wounds and burns, and diabetes.
Studies in animals showed promising results in these areas. For instance, stem cells restored various neurologic deficits including cognitive impairment, improved heart function and vision. In clinical studies with humans, the effects of stem cells in humans were generally less marked compared to those in animals.
Nevertheless, almost all studies found stem cell therapy safe which allows for further research on a larger number of patients.
What are the drawbacks of stem cell therapy?
Several issues slow down the use of stem cells in clinical practice.
The use of human embryonic stem cells provokes ethical, moral, and political debates regarding their potential as human beings. Thus, all efforts are made to replace embryonic stem cells with other types of stem cells, e.g. perinatal or induced pluripotent stem cells. When the use of embryos is deemed necessary, “spare” embryos created during in vitro fertilization procedures may be used.
Embryonic stem cells have a distinct genotype that is different from the individual to whom they are implanted, therefore the immune system of the host attacks them. Not only the stem cells may be destroyed during the process, but exaggerated immune reactions or dysregulation of the immune system may develop.
Due to their ability to divide quickly, stem cells have the potential to induce tumors. In animal studies, embryonic stem cells have induced various tumors, including teratoma (a tumorous cluster of several types of tissues).
Although tumor formation has only incidentally occurred in human studies, researchers are constantly looking for methods to overcome stem cell tumorigenicity.
Patients must be very vigilant when considering any kind of stem cell therapy. Some clinics have taken advantage of public interest in stem cells and used unauthorized stem cell interventions. Such therapies have harmed some patients who experienced vision loss, neurological and organ damage, growth of tumors, bacterial infection, etc.
Both the European Medicines Agency and Federal Drug Administration have issued warnings related to this kind of intervention.
National Institutes of Health. Stem Cell Basics.
International Society for Stem Cell Research. Learn About Stem Cells.
Federal Drug Administration. Warnings About Unauthorized Stem Cell Interventions.
European Medicines Agency. EMA Warns Against Using Unproven Cell-Based Therapies.
Zakrzewski, W., Dobrzynski, M., Szymonowicz, M., Zbigniew, Rybak. (2019). Stem Cells: Past, Present, and Future. BMC.