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Patent Awarded for Skin Stem Cell Regeneration Methods

Human fibroblasts

Human fibroblasts undergoing cell division (Worcester Polytechnic Institute)

24 May 2016. Two faculty members at Worcester Polytechnic Institute in Massachusetts received a patent for techniques that make regeneration of human tissue with adult stem cells more direct and productive. Patent number 9,290,740 was issued by the U.S. Patent and Trademark Office in March 2016 to biomedical engineering professor Raymond Page and biotechnology professor Tanja Dominko, and assigned to Worcester Tech.

Page and Dominko seek to improve on current lab processes for regenerating human tissue from adult stem cells, derived from skin, that they say are inefficient and limited. They study molecular processes behind stem cell differentation or transformation into new cells that repairs damaged tissue, much like amphibians that can grow new limbs after a traumatic injury.

“Our cells have the memory encoded in their DNA of how to create every tissue in the body,” says Dominko in a university statement. “But unlike amphibians, humans and other mammals have lost the ability to regenerate as adults. Instead, we heal injuries with scar formation.”

Their techniques start from fibroblasts — cells found in connective tissue, such as skin — which in most cases have a limited life span outside the body. Attempts to regenerate adult stem cells from fibroblasts, while avoiding ethical questions of embryonic stem cells, usually require adding genes or viruses as well, which runs a risk of an immune response or rejection by the recipient.

The approach by Page and Dominko specified in their patent adds a naturally occurring protein called fibroblast growth factor 2 associated with a range of biological processes, including wound healing. Adding this protein activates a set of dormant stem cell genes in fibroblasts that replicate in a low state of maturity, like progenitor cells, without adding viruses or genes. In addition, this process takes place in a low-oxygen environment. “In our bodies,” says Page, “these cells are exposed to a much lower concentration of oxygen. So what we’re doing is just creating a more natural environment for these cells, and that makes a major difference.”

Among the major differences noted by Page are the much larger number of cells that can be generated, as well as a longer life span. One application of this method generated adult skeletal contracting muscle tissue, while maintaining the ability of original fibroblasts to produce muscle cells for more than 70 generations, compared to about 20 generations using previous culturing techniques. The inventors say this ability to keep producing cells increases the yield a trillion-fold compared to current methods.

“To make cell therapy a realistic clinical treatment,” adds Dominko, “you need a large number of cells in a reasonable time frame, so increasing the yield from cell culture is vital. The idea is to take a patient’s own cells, and grow them under these conditions producing large numbers while maintaining regeneration competence, then return them to that patient as a therapy.”

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