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Wang DR, Wang YH, Pan J, Tian WD. Neurotrophic effects of dental pulp stem cells in repair of peripheral nerve after crush injury. World J Stem Cells 2020; 12:1196-1213. [PMID: 33178401 PMCID: PMC7596440 DOI: 10.4252/wjsc.v12.i10.1196] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 06/13/2020] [Accepted: 08/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nerve diseases and injuries, which are usually accompanied by motor or sensory dysfunction and disorder, impose a heavy burden upon patients and greatly reduce their quality of life. Dental pulp stem cells (DPSCs), derived from the neural crest, have many characteristics that are similar to those of neural cells, indicating that they can be an ideal source for neural repair. AIM To explore the potential roles and molecular mechanisms of DPSCs in crushed nerve recovery. METHODS DPSCs were isolated, cultured, and identified by multilineage differentiation and flow cytometry. Western blot and immunofluorescent staining were applied to analyze the expression levels of neurotrophic proteins in DPSCs after neural induction. Then, we collected the secretions of DPSCs. We analyzed their effects on RSC96 cell proliferation and migration by CCK8 and transwell assays. Finally, we generated a sciatic nerve crush injury model in vivo and used the sciatic function index, walking track analysis, muscle weight, and hematoxylin & eosin (H&E) staining to further evaluate the nerve repair ability of DPSCs. RESULTS DPSCs highly expressed several specific neural markers, including GFAP, S100, Nestin, P75, and NF200, and were inclined toward neural differentiation. Furthermore, neural-induced DPSCs (N-DPSCs) could express neurotrophic factors, including NGF, BDNF, and GDNF. The secretions of N-DPSCs could enhance the proliferation and migration of Schwann cells. In vivo, both DPSC and N-DPSC implants alleviated gastrocnemius muscle atrophy. However, in terms of anatomy and motor function, as shown by H&E staining, immunofluorescent staining, and walking track analyses, the repair effects of N-DPSCs were more sustained, potent, and effective than those of DPSCs and the controls. CONCLUSION In summary, this study demonstrated that DPSCs are inclined to differentiate into neural cells. N-DPSCs express neurotrophic proteins that could enhance the proliferation and migration of SCs. Furthermore, our results suggested that N-DPSCs could help crushed nerves with functional recovery and anatomical repair in vivo. Thus, DPSCs or N-DPSCs could be a promising therapeutic cell source for peripheral nerve repair and regeneration.
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Affiliation(s)
- Dian-Ri Wang
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Hao Wang
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jian Pan
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China.
| | - Wei-Dong Tian
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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Wu S, Chen MS, Maurel P, Lee YS, Bunge MB, Arinzeh TL. Aligned fibrous PVDF-TrFE scaffolds with Schwann cells support neurite extension and myelination in vitro. J Neural Eng 2018; 15:056010. [PMID: 29794323 DOI: 10.1088/1741-2552/aac77f] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVE Polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE), which is a piezoelectric, biocompatible polymer, holds promise as a scaffold in combination with Schwann cells (SCs) for spinal cord repair. Piezoelectric materials can generate electrical activity in response to mechanical deformation, which could potentially stimulate spinal cord axon regeneration. Our goal in this study was to investigate PVDF-TrFE scaffolds consisting of aligned fibers in supporting SC growth and SC-supported neurite extension and myelination in vitro. APPROACH Aligned fibers of PVDF-TrFE were fabricated using the electrospinning technique. SCs and dorsal root ganglion (DRG) explants were co-cultured to evaluate SC-supported neurite extension and myelination on PVDF-TrFE scaffolds. MAIN RESULTS PVDF-TrFE scaffolds supported SC growth and neurite extension, which was further enhanced by coating the scaffolds with Matrigel. SCs were oriented and neurites extended along the length of the aligned fibers. SCs in co-culture with DRGs on PVDF-TrFE scaffolds promoted longer neurite extension as compared to scaffolds without SCs. In addition to promoting neurite extension, SCs also formed myelin around DRG neurites on PVDF-TrFE scaffolds. SIGNIFICANCE This study demonstrated PVDF-TrFE scaffolds containing aligned fibers supported SC-neurite extension and myelination. The combination of SCs and PVDF-TrFE scaffolds may be a promising tissue engineering strategy for spinal cord repair.
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Affiliation(s)
- Siliang Wu
- Materials Science and Engineering Program, New Jersey Institute of Technology, Newark, NJ 07102, United States of America
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