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Mol Neurobiol. 2018 Aug;55(8):6965-6983. doi: 10.1007/s12035-018-0913-3. Epub 2018 Jan 25.

Neural Crest Stem-Like Cells Non-genetically Induced from Human Gingiva-Derived Mesenchymal Stem Cells Promote Facial Nerve Regeneration in Rats.

Author information

1
Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, PA, 19104, USA.
2
Division of Plastic and Reconstructive Surgery, University of Pennsylvania Perelman School of Medicine, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA.
3
Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, 3320 Smith Walk, Philadelphia, PA, 19104, USA.
4
Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, PA, 19104, USA. Anh.Le@uphs.upenn.edu.
5
Department of Oral and Maxillofacial Surgery, Penn Medicine Hospital of the University of Pennsylvania, Perelman Center for Advanced Medicine, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA. Anh.Le@uphs.upenn.edu.

Abstract

Non-genetic induction of somatic cells into neural crest stem-like cells (NCSCs) is promising for potential cell-based therapies for post-traumatic peripheral nerve regeneration. Here, we report that human gingiva-derived mesenchymal stem cells (GMSCs) could be reproducibly and readily induced into NCSCs via non-genetic approaches. Compared to parental GMSCs, induced NCSC population had increased expression in NCSC-related genes and displayed robust differentiation into neuronal and Schwann-like cells. Knockdown of the expression of Yes-associated protein 1 (YAP1), a critical mechanosensor and mechanotransducer, attenuated the expression of NCSC-related genes; specific blocking of RhoA/ROCK activity and non-muscle myosin II (NM II)-dependent contraction suppressed YAP1 and NCSC-related genes and concurrently abolished neural spheroid formation in NCSCs. Using a rat model of facial nerve defect, implantation of NCSC-laden nerve conduits promoted functional regeneration of the injured nerve. These promising findings demonstrate that induced NCSCs derived from GMSCs represent an easily accessible and promising source of neural stem-like cells for peripheral nerve regeneration.

KEYWORDS:

Facial nerve regeneration; Gingiva-derived mesenchymal stem cells; Neural crest stem cells; RhoA/ROCK; YAP1

PMID:
29372546
DOI:
10.1007/s12035-018-0913-3

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