Creating Stem Cells without Gene Editing
A new study from the University of Buffalo has demonstrated that adult skin cells can be reprogrammed into a type of stem cell without the need for genetic engineering. Once formed, these stem cells, known as neural crest (NC) cells, can differentiate into cell types present in the spinal cord and brain and be used to either form cell lines for disease study in vitro, or as regenerative cures in patients. The research was published in Stem Cells.
The study treated postnatal human epidermal keratinocytes with fibroblast growth factor 2 and insulin-like growth factor 1 signals to examine the effect they had on the cells’ biology. Genome-wide transcriptome analyses were able to show that the keratinocyte-derived NC cells were similar to those derived from human embryonic stem cells. The identification of the derived cells was further confirmed by inserting the NC cells into chicken embryos and demonstrating that they acted in the same way as natural NC cells.
In the past, adult cells have been used to create stem cells but it has always required the insertion of new DNA into the genome. This novel technique doesn’t rely on the insertion of foreign DNA, making their production independent from tools such as CRISPR or TALENs.
Once the reprogramming process is complete, the NC cells can differentiate into melanocytes, neurons, Schwann cells (part of the nervous system which produce myelin), or mesenchymal cells.
“In medical applications this has tremendous potential because you can always get a skin biopsy,” said Professor Stelios T. Andreadis, Ph.D., Chair of the Department of Chemical and Biological Engineering at the University of Buffalo. “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.”
Alongside patient treatment, the technique may also be of use in the creation of disease models. Skin cells are much easier to obtain from patients with genetic diseases in their nervous system than natural NC cells, however, the skin cells will not express the mutated genes. Converting skin cells into NC cells will reactivate the dormant mutated genes, which can then be differentiated into Schwann cells or neurons and used to form cell lines to study the disease in vitro.
The research has recently received a grant from the National Institutes of Health amounting to $1.7 million. The team hope to use the money to better understand the underlying mechanisms behind the reprogramming of the cell and to use mouse models to begin the early stages formulating a clinical treatment for Parkinson’s Disease.
“This work has the potential to provide a novel source of abundant, easily accessible and autologous cells for treatment of devastating neurodegenerative diseases. We are excited about this discovery and its potential impact and are grateful to NIH for the opportunity to pursue it further,” Andreadis said.