A new approach to repairing peripheral nerves marries the regenerating power of gingiva-derived mesenchymal stem cells with a biological scaffold to enable the functional recovery of nerves following a facial injury, according to a study by a cross-disciplinary team from the University of Pennsylvania School of Dental Medicine and Perelman School of Medicine.
Faced with repairing a major nerve injury to the face or mouth, skilled surgeons can take a nerve from an arm or leg and use to it restore movement or sensation to the original site of trauma. This approach, known as a nerve autograft, is the standard of care for nerve repair, but has its shortcomings. Besides taking a toll on a previously uninjured body part, the procedure doesn’t always result in complete and functional nerve regrowth, especially for larger injuries.
Scientists and clinicians have recently been employing a different strategy for regrowing functional nerves involving commercially-available scaffolds to guide nerve growth. In experimental approaches, these scaffolds are infused with growth factors and cells to support regeneration. But to date, these efforts have not been completely successful. Recovery can fall short due to a failure to coax large numbers of regenerating axons to cross the graft and then adequately mature and regrow myelin, the insulating material around peripheral nerves that allows them to fire quickly and efficiently.
In an innovative approach to guided nerve repair, shared in the journal npj Regenerative Medicine, the Penn team coaxed human gingiva-derived mesenchymal stem cells (GMSCs) to grow Schwann-like cells, the pro-regenerative cells of the peripheral nervous system that make myelin and neural growth factors. The current work demonstrated that infusing a scaffold with these cells and using them to guide the repair of facial nerve injuries in an animal model had the same effectiveness as an autograft procedure
Le and colleagues led by Qunzhou Zhang, now a faculty member at Penn Dental Medicine, were able to apply their previous understanding of GMSCs to grow them in a collagen matrix using specific conditions that encouraged the cells to grow more like Schwann cells, the cells’ identity confirmed with a variety of genetic markers.
To move the work forward, Le reached out to the Perelman School of Medicine’s D. Kacy Cullen, a bioengineer who has worked on nerve repair for 15 years. Cullen and colleagues have expertise in creating and testing nerve scaffold materials.
“To get host Schwann cells all throughout a bioscaffold, you’re basically approximating natural nerve repair,” Cullen says. Indeed, when Le and Cullen’s groups collaborated to implant these grafts into rodents with a facial nerve injury and then tested the results, they saw evidence of a functional repair. The animals had less facial droop than those that received an “empty” graft and nerve conduction was restored. The implanted stem cells also survived in the animals for months following the transplant.
While the current study worked at repairing a small gap in a nerve, the researchers aim to continue refining the method to try to repair larger gaps, as often arise when oral cancer necessitates surgical removal of a tumor. “The field desperately needs what have been dubbed ‘living scaffolds’ to direct the regrowth,” Cullen says.
Qunzhou Zhang, Phuong Nguyen, Justin C. Burrell, Jincheng Zeng, Shihong Shi, Rabie M. Shanti, Grace Kulischak, D. Kacy Cullen, Anh D. Le. Harnessing 3D collagen hydrogel-directed conversion of human GMSCs into SCP-like cells to generate functionalized nerve conduits. npj Regenerative Medicine, 2021; 6 (1) DOI: 10.1038/s41536-021-00170-y
University of Pennsylvania. (2021, October 8). Nerve repair, with help from stem cells. ScienceDaily. Retrieved January 27, 2023 from www.sciencedaily.com/releases/2021/10/211008083546.htm