title: Chitosan scaffolds induce human dental pulp stem cells to neural differentiation: potential roles for spinal cord injury therapy.
abstract: Cell-based transplantation strategies hold great potential for spinal cord injury (SCI) repair. Chitosan scaffolds have therapeutic benefits for spinal cord regeneration. Human dental pulp stem cells (DPSCs) are abundant available stem cells with low immunological incompatibility and can be considered for cell replacement therapy. The purpose of this study is to investigate the role of chitosan scaffolds in the neural differentiation of DPSCs in vitro and to assess the supportive effects of chitosan scaffolds in an animal model of SCI. DPSCs were incubated with chitosan scaffolds. Cell viability and the secretion of neurotrophic factors were analyzed. DPSCs incubated with chitosan scaffolds were treated with neural differentiation medium for 14 days and then neural genes and protein markers were analyzed by Western blot and reverse transcription plus the polymerase chain reaction. Our study revealed a higher cell viability and neural differentiation in the DPSC/chitosan-scaffold group. Compared with the control group, the levels of BDNF, GDNF, b-NGF, and NT-3 were significantly increased in the DPSC/chitosan-scaffold group. The Wnt/β-catenin signaling pathway played a key role in the neural differentiation of DPSCs combined with chitosan scaffolds. Transplantation of DPSCs together with chitosan scaffolds into an SCI rat model resulted in the marked recovery of hind limb locomotor functions. Thus, chitosan scaffolds were non-cytotoxic and provided a conducive and favorable microenvironment for the survival and neural differentiation of DPSCs. Transplantation of DPSCs might therefore be a suitable candidate for treating SCI and other neuronal degenerative diseases.
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.
authors.forename: Guijuan
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Bao
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Cardiology Medical, Tongzhou First People's Hospital, Nantong, Jiangsu Province, 226300, China.
authors.forename: Yuanzhou
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China. fengxingmeint@126.com.
authors.forename: Xingmei
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China. cuizhiming2012@hotmail.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000293:Adolescent; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D048271:Chitosan / Q000494:pharmacology*; D003782:Dental Pulp / Q000166:cytology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D054457:Tissue Scaffolds / Q000737:chemistry*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D051176:beta Catenin; D048271:Chitosan; D053148:Caspase 3
keywords: Chitosan scaffolds; Dental pulp stem cells (DPSCs); Neural differentiation; Spinal cord injury (SCI); Wnt/β-catenin