Therapeutic Use of Embryonic Stem Cells
Human embryonic stem cells and their derivatives have many of the same potential therapeutic uses as adult stem cells. They could be used to replace or restore tissue damaged by disease or injury. However, at this point in time, human therapies based on the application of embryonic stem cells are still experimental. Those working in the Weld generally maintain that research on these sorts of stem cells has not reached the stage at which it can be attempted in humans. Even so, many current embryonic stem cell investigations are geared toward exploring possible future cures for certain diseases. For instance, some researchers are attempting to produce neurons from human embryonic stem cells in order to treat persons with Parkinson’s disease and to elicit pancreatic cells producing insulin to transplant into those with diabetes.
However, many scientists agree that clinical trials of human embryonic stem cells for these conditions and others, such as amyotrophic lateral sclerosis and multiple sclerosis, are not likely to take place for at least five or—more likely—ten years. Other scientists argue that animal studies indicate that certain human embryonic stem cell treatments might be effective for repairing damaged cells in patients sooner than that. Geron Corporation in Menlo Park, California, plans to begin treatment of those with spinal cord injuries by means of human embryonic stem cells sometime in 2007. This work, based on research by Hans Keirstead of the University of California at Irvine and his colleagues, is designed to ameliorate but not cure such injuries. One of its purposes is to display the safety of using human embryonic stem cell therapies in humans. However, as was the case with adult stem cell research, here, too, researchers disagree about whether sufficient work has been done in animals to justify moving this research to clinical efforts with human beings.
Advantages and Limitations
A significant advantage that human embryonic stem cells offer is that they can be multiplied over long periods of time in the laboratory—in principle, indefinitely. One group of embryonic stem cells, after proliferating in the laboratory for several months, can provide millions of cells. Moreover, embryonic stem cells can differentiate into a wide range of cell types and can regenerate all normal cell types found in the body. Their extreme flexibility and capacity for growth appear to make them ideal for producing large quantities of cells to treat many diseases and injuries. Yet research on human embryonic stem cells is at a relatively early stage, and there are still numerous barriers that stem cell investigators must overcome before the promise of this research might be realized. It is difficult to derive and maintain embryonic stem cells. The molecular mechanisms that underlie their self-renewal are unknown. They can be hard to study in a living system. when tested in animals, these cells have at times differentiated into the wrong cells or migrated away from the insertion site.
Perhaps the most serious problem associated with the therapeutic use of embryonic stem cells in humans is that, if they are transferred to patients, these cells might grow into unwanted tissue or cancerous tumors. Studies indicate that if embryonic stem cells that have not begun to differentiate are injected into mice with compromised immune systems, a benign tumor known as a teratoma with rapidly growing cells of several differentiated cell types can develop. This would clearly be undesirable if such stem cells were transplanted into patients. Since it is undifferentiated embryonic stem cells (but not the specialized cells that are developed from them) that have been shown to induce teratomas, it has been hypothesized that such tumor formation might be avoided by removing any undifferentiated embryonic cells from the groups of such cells that are to be inserted into patients. Only the more specialized cells into which embryonic stem cell differentiate, such as skin and pancreas cells, stem cell scientists currently think, should be considered for therapy in humans. This would reduce the risk that tumors might develop in patients.
Another significant problem that those attempting to use embryonic stem cells for therapeutic purposes have to confront is that of immune rejection. Because embryonic stem cells will not ordinarily have been derived from the specific patient to be treated, there is a risk that they will be rejected by that patient’s immune system. Scientists have proposed several different ways of avoiding this difficulty. These include using research cloning (somatic cell nuclear transfer) procedures to generate human embryonic stem cells that are genetically identical to those of the person receiving the transplant, genetically engineering the embryonic stem cells to express certain antigens of the recipient that would counter any possible immune reaction, or developing ‘‘universal’’ donor stem cell lines that could be used in many different patients. However, each of these methods has its drawbacks.
Many of the embryonic stem cell lines currently available for research, including all of those approved for use in federally funded research under the Bush policy as of this writing, were cultured on mouse feeder cells layers that promote proliferation. However, there is significant evidence that these lines are contaminated with sialic acid from mice, which produces an immune reaction, and with mouse viruses. These factors could make them unsafe to use in clinical applications in human beings. In 2005, scientists tested five human embryonic stem cell lines that had been nurtured on mouse feeder cells, along with several cultures of mouse feeder cells for signs of mouse retroviruses and found no evidence of such viruses. Although their study suggests that stem cell lines established on mouse feeder layers might be free from viruses, it does not overcome the problem of the contamination of human embryonic stem cell lines cultured on mouse feeders with sialic acid. Therefore, it is preferable to use feeder cells that do not contain animal products to avoid this difficulty.
Scientists have attempted to overcome the contamination problem by developing new methods of culturing human embryonic stem cells that do not require mouse feeder cells. Some have developed human components for this purpose, while others have employed cells derived from differentiated human embryonic stem cells. Still others have used mouse extracellular matrix components, rather than whole mouse cells, to culture human embryonic stem cells. Such measures have allowed them to develop some human embryonic stem cell lines that are free of animal contamination.