title: The effects of controlled release of neurotrophin-3 from PCLA scaffolds on the survival and neuronal differentiation of transplanted neural stem cells in a rat spinal cord injury model.
abstract: Neural stem cells (NSCs) have emerged as a potential source for cell replacement therapy following spinal cord injury (SCI). However, poor survival and low neuronal differentiation remain major obstacles to the use of NSCs. Biomaterials with neurotrophic factors are promising strategies for promoting the proliferation and differentiation of NSCs. Silk fibroin (SF) matrices were demonstrated to successfully deliver growth factors and preserve their potency. In this study, by incorporating NT-3 into a SF coating, we successfully developed NT-3-immobilized scaffolds (membranes and conduits). Sustained release of bioactive NT-3 from the conduits for up to 8 weeks was achieved. Cell viability was confirmed using live/dead staining after 14 days in culture. The efficacy of the immobilized NT-3 was confirmed by assessing NSC neuronal differentiation in vitro. NSC neuronal differentiation was 55.2 ± 4.1% on the NT-3-immobilized membranes, which was significantly higher than that on the NT-3 free membrane. Furthermore, 8 weeks after the NSCs were seeded into conduits and implanted in rats with a transected SCI, the conduit+NT-3+NSCs group achieved higher NSC survival (75.8 ± 15.1%) and neuronal differentiation (21.5 ± 5.2%) compared with the conduit+NSCs group. The animals that received the conduit+NT-3+NSCs treatment also showed improved functional outcomes, as well as increased axonal regeneration. These results indicate the feasibility of fabricating NT-3-immobilized scaffolds using the adsorption of NT-3/SF coating method, as well as the potential of these scaffolds to induce SCI repair by promoting survival and neuronal differentiation of transplanted NSCs.
authors.affiliation: Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Pain Medicine, Shenzhen Nanshan Hospital, Shenzhen, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liao
authors.affiliation: Department of Orthopaedics, Mianyang Center Hospital, Mianyang, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, Guangdong hospital of traditional Chinese medicine, Guangzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Fuxing
authors.initials: F
authors.lastname: Pei
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D020933:Neurotrophin 3 / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D051381:Rats; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D058630:Spinal Cord Regeneration; D054457:Tissue Scaffolds
chemical_list: D055767:Immobilized Proteins; D020933:Neurotrophin 3