Umbilical cord stem cells (UCSCs) have been differentiated into clinically significant cell types that might, potentially, lead to new treatment options for spinal cord injuries, multiple sclerosis, and other nervous system diseases.
James Hickman, a University of Central Florida bioengineer and leader of the research group that accomplished this work, said, “This is the first time this has been done with non-embryonic stem cells. . . . We’re very excited about where this could lead because it overcomes many of the obstacles present with embryonic stem cells.” Hickman’s work and that of his colleagues was published in the Jan. 18 issue of the journal ACS Chemical Neuroscience.
UCSCs do not pose the ethical dilemma represented by embryonic stem cells (ESCs). ESC lines are made from 5-day old human embryos and in order to derive them, the inner cell mass cells are extracted from the embryo by means of destroying the embryo. Destruction of a human embryo ends the life of a very young human person. UCSCs, however, come from a source that would otherwise be discarded, and the acquisition of UCSCs do not compromise the life of a human person. Another major benefit is that umbilical cells generally are not rejected by the immune system, and this simplifies their potential use in medical treatments.
The Menlo, California-based pharmaceutical company, Geron, developed a treatment protocol for spinal cord repair that utilized oligodendrocyte precursor cells that were derived from embryonic stem cells. However, it took Geron scientists 18 months to secure approval from the Food & Drug Administration (FDA) for human clinical trials. This is due, largely, to the ethical and public concerns attached to human ESCs. These concerns, in addition to anxieties over ESC-caused tumors, led the company to shut down its ESC division. This highlights the need for other stem cell alternatives.
One of the greatest challenges in working with any kind of stem cell is determining the precise chemical or biological cues that trigger them to differentiate into the desired cell type. The lead author on this paper, Hedvika Davis, a postdoctoral researcher in Hickman’s lab, transformed UCSCs into oligodendrocytes (those structural cells that surround and insulate nerves in the brain and spinal cord). Davis learned from research done by other groups that surface proteins on the surfaces of oligodendrocytes bind the hormone/neurotransmitter norepinephrine. This suggests that cells normally interact with this chemical and that it might be one of the factors that stimulates oligodendrocyte production. Therefore Davis decided to treat USCSs with epinephrine as a starting point.
In early tests, Davis found that norepinephrine, plus several other stem cell growth promoters, caused the UCSCs to differentiate into oligodendrocytes. However, that conversion was incomplete, since the cells grew but stopped short of becoming completely mature oligodendrocytes. Clearly something else was needed to push UCSCs completely into mature oligodendrocytes.
Many stem cells differentiate into particular cell types only if the appropriate environment is offered to them. For example, mesenchymal stem cells can form cartilage, but cartilage formation is extremely sensitive to environmental factors like cell density, and the matrix in which cells are embedded. Thus, Davis decided that, in addition to chemistry, the physical environment might be critical. In order to more closely approximate the physical restrictions cells face in the body, Davis constructed a more confined, three-dimensional environment. She grew the cells on a microscope slide, covered by a glass cover slip. Once the UCSCs had the proper confined environment and norepinephrine plus the appropriate growth factors, they differentiated into completely mature oligodendrocytes. Davis noted, “We realized that the stem cells are very sensitive to environmental conditions.”
The use of these differentiated oligodendrocytes is exciting. There are two main options for the use of these cells. First, the cells could be injected into the body at the point of a spinal cord injury to promote repair. Another intriguing possibility for the Hickman team’s work relates to multiple sclerosis and similar conditions. Hickman explained, “Multiple sclerosis is one of the holy grails for this kind of research.” Hickman’s research group is collaborating with Stephen Lambert at UCF’s medical school, another of the paper’s authors, to explore biomedical possibilities.
Oligodendrocytes produce a protein called myelin, which insulates nerve cells. Myelin sheaths make is possible for neurons in the central nervous system to conduct those nerve impulses that guide movement and other functions. Myelin loss is responsible for conditions like multiple sclerosis, and is also observed in other related conditions such as diabetic neuropathy.
The injection of new, healthy oligodendrocytes might improve the condition of patients suffering from such neurological diseases. These research teams are also hoping to develop the techniques needed to grow oligodendrocytes in the lab and use them a model system to better understand the loss and restoration of myelin, and for testing potential new treatments. Hickman enthusiastically said, “We want to do both. We want to use a model system to understand what’s going on and also to look for possible therapies to repair some of the damage, and we think there is great potential in both directions.”