Stelios Andreadis, PhD.

Stelios Andreadis, PhD, is leading a team of researchers who have discovered how to convert adult skin cells into stem cells without modifying their genetics.

Neural Crest Stem Cells From Skin Without Genetic Modifications

Published March 27, 2017

UB researchers have found that adult skin cells can be converted into neural crest cells without any genetic modification.

“In medical applications this has tremendous potential because you can always get a skin biopsy.”
Professor of biomedical engineering

The discovery, which was several years in the making, proves that these stem cells can yield other cells that are present in the spinal cord and brain.

May Spur Regenerative Cures from Patient’s Own Cells

The applications could be very significant, ranging from studying genetic diseases in a dish to generating possible regenerative cures from a patient’s own cells.

“It’s actually quite remarkable that it happens,” says Stelios Andreadis, PhD, professor of biomedical engineering, who recently published a paper on the results, titled “Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates,” 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.

Reprogramming Cells Without Genetic Modification

Stem cells have been derived from adult cells before, but not without adding genes to alter the cells. The new process yields neural crest cells without addition of foreign genetic material. The reprogrammed neural crest cells can become smooth muscle cells, melanocytes, Schwann cells or neurons.

“In medical applications this has tremendous potential because you can always get a skin biopsy,” says Andreadis, who is also professor and chair of the Department of Chemical and Biological Engineering in the School of Engineering and Applied Sciences.

“We can grow the cells to large numbers and reprogram them without genetic modification. So, autologous cells derived from the patient can be used to treat devastating neurogenic diseases that are currently hampered by the lack of easily accessible cell sources,” he says.

Neural crest stem cells.

This image shows Keratinocyte-derived neural crest stem cells turning into neurons as shown by typical neuronal morphology.  

Process Allows for Modeling of Disease

The process can also be used to model disease. Skin cells from a person with a genetic disease of the nervous system can be reprogrammed into neural crest cells. These cells will have the disease-causing mutation in their chromosomes, 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 reprogramming to the pluripotent state.

Collaborators Contributed Wide Range of Expertise

The discovery was a gradual process, taking almost five years, Andreadis says, as successive experiments kept leading to something new.

“It was one step at a time. It was a very challenging task that involved a wide range of expertise and collaborators to bring it to fruition,” he says.

Collaborators include:

  • Gabriela K. Popescu, PhD, professor of biochemistry in the Jacobs School of Medicine and Biomedical Sciences
  • Song Liu, PhD, vice chair of biostatistics and bioinformatics at Roswell Park Comprehensive Cancer Center and a research associate professor in biostatistics in UB’s School of Public Health and Health Professions
  • Marianne Bronner, PhD, professor of biology and biological engineering, California Institute of Technology

Andreadis credits the persistence of his then-doctoral student, Vivek K. Bajpai, for sticking with it.

“He is an excellent and persistent student,” Andreadis says. “Most students would have given up.”

Studying Mechanisms Occurring as Cells Reprogram

The research was supported by grants from the National Institutes of Health (NIH).

Andreadis also credits a seed grant from UB’s Office of the Vice President for Research and Economic Development’s IMPACT program that enabled part of the work.

The work recently received a $1.7 million NIH grant to delve into the mechanisms that occur as the cells reprogram, and to employ the cells for treating the Parkinson’s-like symptoms in a mouse model of hypomyelinating disease.

“This work has the potential to provide a novel source of abundant, easily accessible and autologous cells for treatment of devastating neurodegenerative diseases,” Andreadis says. “We are excited about this discovery and its potential impact and are grateful to NIH for the opportunity to pursue it further.”