title: Neurotrophin-3 gene-modified Schwann cells promote TrkC gene-modified mesenchymal stem cells to differentiate into neuron-like cells in poly(lactic-acid-co-glycolic acid) multiple-channel conduit.
abstract: Rapid progress in the field of nerve tissue engineering has opened up the way for new therapeutic strategies for spinal cord injury (SCI). Bone marrow-derived mesenchymal stem cells (MSCs) could be differentiated into neural lineages, which can be used as a potential cell source for nerve repair. Schwann cells (SCs) have been reported to support structural and functional recovery of SCI. In this study, we co-cultured neurotrophin-3 (NT-3) gene-modified SCs and NT-3 receptor tyrosine protein kinase C (TrkC) gene-modified MSCs in a three-dimensional porous poly(lactic-acid-co-glycolic acid) (PLGA) conduit with multiple channels in vitro for 14 days. Our results showed that more than 50% of the grafted MSCs were MAP2- and β-III-tubulin-positive cells, and the MSCs expressed a high level of β-III-tubulin detected by Western blotting, indicating a high rate of neuronal differentiation. Furthermore, immunostaining of PSD95 revealed the formation of a synapse-like structure, which was confirmed under electron microscopy. In conclusion, co-culture of NT-3 gene-modified SCs and TrkC gene-modified MSCs in the PLGA multiple-channeled conduit can promote MSCs' differentiation into neuron-like cells with synaptogenesis potential. Our study provides a biological basis for future application of this artificial MSCs/SCs/PLGA complex in the SCI treatment.
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yan-qing
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Liu-min
authors.initials: LM
authors.lastname: He
authors.forename: Bin
authors.initials: B
authors.lastname: Xing
authors.forename: Xiang
authors.initials: X
authors.lastname: Zeng
authors.forename: Chen-guang
authors.initials: CG
authors.lastname: Zeng
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Da-ping
authors.initials: DP
authors.lastname: Quan
authors.forename: Yuan-shan
authors.initials: YS
authors.lastname: Zeng
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D018920:Coculture Techniques; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019344:Lactic Acid / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics* / Q000378:metabolism; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D020812:Receptor, trkC / Q000235:genetics* / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D054457:Tissue Scaffolds
chemical_list: D015415:Biomarkers; D020933:Neurotrophin 3; D049452:Green Fluorescent Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020812:Receptor, trkC