As clinical stage research involving stem cells has expanded during the past decade, so has public debate regarding the relative advantages and disadvantages of embryonic versus adult stem cells. Ethical concerns about the use of embryonic stem cells have dominated much of this discussion. Recently, attention has shifted toward efforts to make adult stem cells more versatile and share more of the advantages of embryonic cells, which can differentiate into any human cell types.
Researchers have made important advances in their ability to manipulate adult cells. For example, scientists from the University of Cambridge’s Institute for Medical Research reprogrammed skin cells to behave like liver cells so that we can better understand the mechanisms of different liver diseases and more easily identify optimal targets for therapeutic drugs. While these efforts may open up new avenues of research, there have been some challenges in administering these cells in humans. Studies have found that the reprogramming process in adult stem cells may increase the risk of tumors. In some cases, reprogrammed cells appear to retain the memory of their original cell activity, which could make their behavior unpredictable. When researchers at the Children’s Hospital in Boston tried to transform blood cells into tissue cells, they reverted back to blood cells soon after.
By contrast, therapies derived from adult stem cells that have not been reprogrammed appear to have a lower potential to form tumors. Most adult stem cell therapies in clinical development incorporate cells from bone marrow, umbilical cord blood, skin or gut. These cells have been shown in numerous studies to be relatively safe and have now been used to treat different diseases in more than 50,000 people around the world. Aastrom’s lead product candidate, ixmyelocel-T, which is derived from a patient’s own adult bone marrow stem cells, has been tested safely in more than 200 patients.
In addition to evaluating the advantages and disadvantages of therapies derived from embryonic and adult stem cells, researchers are also exploring two different methods of stem cell transplantation. Some stem cell therapies are allogeneic, meaning that cells are taken from a donor, processed, and then used to treat one or more patients. These types of therapies carry the risk of graft-versus-host disease, which occurs when the donor’s transplanted stem cells attack the recipient’s body tissues. An allogeneic transplant also has the potential to transfer pathogens that cause disease or illness from a donor to a recipient.
With autologous therapies, patients receive cells that come from their own body, which virtually eliminates the risk of graft-versus-host disease or the introduction of new pathogens. This characteristic of ixmyelocel-T helps to eliminate the risk of rejection and the need to treat patients with immunosuppressive therapy before or after administration. In our proprietary production process for ixmyelocel-T, we work to expand the populations of certain cells found in bone marrow that are known to play a role in repairing tissue, restoring blood flow and reducing inflammation. Findings from our clinical research thus far indicate that ixmyelocel-T has the potential to produce long-term engraftment and tissue repair.
Cell therapies have the potential to substantially improve the lives of patients affected by poorly treated chronic diseases. Well-designed and well-controlled clinical trials will enable us to evaluate the relative risks and benefits of these therapies and realize their therapeutic potential.