Summary: A discovery, several years in the making, demonstrates that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic modification, and that these stem cells can yield other cells that are present in the spinal cord and the brain. The applications could be significant, from studying genetic diseases in a dish to generating possible regenerative cures from the patient’s own cells.
The practical implications could be very significant from studying genetic diseases in a lab to finding possible cures from patient’s own cells. “It’s actually quite remarkable that it happens,” says Stelios T. Andreadis, PhD, professor and chair of UB’s Department of Chemical and Biological Engineering, who recently published a paper on the results in the journal Stem Cells. The identity of the cells was further confirmed by lineage tracing experiments, where the reprogrammed cells were implanted in chicken embryos and acted just as neural crest cells do.
Stem cells were derived from adult cells even before, but not without adding genes to alter the cells. The new process gives neural crest cells without addition of foreign genetic material. The reprogrammed neural crest cells can become smooth muscle cells, melanocytes, Schwann cells or neurons.
Practical applications:
This has tremendous application in medicine because you could always get a skin biopsy. We can grow these cells to large numbers, reprogram them without genetic modification. This can be used to treat patients with neurogenic diseases that are hampered by the lack of easily accessible cell sources.
This process can also be used to model disease. Skin cells derived from a person with genetic disease of the nervous system can be reprogrammed into neural crest cells. These would have the disease causing mutation in their chromosome, but the genes that cause the mutation are not expressed in the skin. . The genes are likely to be expressed when cells differentiate into neural crest lineages, such as neurons or Schwann cells, thereby enabling researchers to study the disease in a dish. This is similar to induced pluripotent stem cells, but without genetic modification or reprograming to the pluripotent state.
The discovery was a gradual process, Andreadis says, as successive experiments kept leading to something new. “It was one step at a time. It was a very challenging task that took almost five years and involved a wide range of expertise and collaborators to bring it to fruition,” Andreadis says. Collaborators include Gabriella Popescu, PhD, professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB; Song Liu, PhD, vice chair of biostatistics and bioinformatics at Roswell Park Cancer Institute and a research associate professor in biostatistics UB’s School of Public Health and Health Professions; and Marianne Bronner, PhD, professor of biology and biological engineering, California Institute of Technology.
Andreadis credits the persistence of his then-PhD student, Vivek K. Bajpai, for sticking with it.
As quoted by Andreadis, this work has the potential to provide a novel source of abundant autologous cells for treatment of neurodegenerative diseases.