Application of NSC-like Progenitors Induced from Gingiva-derived MSCs in Facial Nerve Regeneration
Dr. Qunzhou Zhang received his PhD in Biochemistry and Molecular Biology from West China University of Medical Sciences in 2000. He is currently a senior investigator and the leading scientist in Dr. Anh Le’s laboratory at the Department of Oral & Maxillofacial Surgery, University of Pennsylvania School of Dental Medicine. The primary focus of Dr. Zhang’s current research is immunomodulatory and regenerative function of human gingiva-derived mesenchymal stem cells. His research is funded by Stephan B. Milam Research Support Grant from Oral & Maxillofacial Surgery Foundation, University of Pennsylvania Diabetes Research Center (DRC) and Schoenleber Pilot Grant from Penn School of Dental Medicine.
Fully functional recovery of facial nerve injury is a major challenge for oral surgeons. Autologous nerve grafts currently remain the gold standard for repairing injured peripheral nerves with a large gap. However, donor site morbidity, availability of donor nerve and danger of neuroma formation significantly impede their clinic application. Even though alternative allogenic grafts and bioengineered nerve conduits are used in clinic, their overall outcomes are still suboptimal. The combination of bioengineered nerve conduits and stem cells is emerging as a novel approach for peripheral nerve regeneration. Neural stem (NSC) or progenitor cells are considered an ideal candidate seed cell source for stem cell-based treatment of nerve injury, but it remains a challenge to get enough transplantable NSCs for clinical application. Expandable and multipotent neural progenitor cells (NPCs) can be induced from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), but the process is complicated and time-consuming and needs the introduction of exogenous genes, which raise concerns regarding the safety for their clinical use. Thus, generation of expandable NPC-like cells directly from somatic cells may represent an ideal approach for stem cell-based therapy of peripheral nerve injury. This work will test the hypothesis that human gingiva-derived mesenchymal stem cells (GMSCs) can be directly converted to multipotent NPC-like cells with therapeutic potentials for facial nerve defects. Specifically, we will optimize the culture conditions for induction of NPC-like cells from GMSCs and evaluate their multipotency both in vitro and in vivo. We will then use a rat model to test the therapeutic efficacy of GMSC-derived NPC-like cells on repair/regeneration of facial nerve defects. Accomplishment of this study will provide substantial evidence for the potential clinical application of GMSC-derived NPC-like cells for facial nerve regeneration.
1. Zhang Q, Nguyen P, Xu Q, Park W, Lee S, Furuhashi A, Le AD. Neural Progenitor-Like Cells Induced from Human Gingiva-Derived Mesenchymal Stem Cells Regulate Myelination of Schwann Cells in Rat Sciatic Nerve Regeneration. Stem Cells Transl Med. 2017 Feb;6(2):458-470. doi: 10.5966/sctm.2016-0177 PMID: 27604215 Full Text
2. Zhang Q, Nguyen PD, Shi S, Burrell JC, Xu Q, Cullen KD, Le AD. Neural Crest Stem-Like Cells Non-genetically Induced from Human Gingiva-Derived Mesenchymal Stem Cells Promote Facial Nerve Regeneration in Rats. Mol Neurobiol. 2018 Jan 25. doi: 10.1007/s12035-018-0913-3. [Epub ahead of print] PMID: 29372546 Full Text
3. Qunzhou Zhang, Phuong Nguyen, Shihong Shi, Justin Burrell, Kacy Cullen, Anh D. Le. 3D Bioprinted Scaffold-free Nerve Constructs with Human Gingiva-derived Mesenchymal Stem Cells as Bioink Promote Rat Facial Nerve Regeneration. Full Text
Abstracts, Posters & Oral Presentation:
1. Qin Mao, Qunzhou Zhang, Neeraj Panchal, Pasha Shakoori, Anh D. Le. Human Gingiva-Derived Mesenchymal Stem Cells Regulate Myelination of Schwann Cells via EGR2/Krox20 Pathway. 46th AADR/95th IADR, 2017 March 22-25, San Francisco, California., USA