title: Bone marrow-derived mesenchymal stem cells in three-dimensional culture promote neuronal regeneration by neurotrophic protection and immunomodulation.
abstract: Accumulating evidence has revealed three-dimensional (3D) culture could better mimic the stem cell niche in vivo in comparison with conventional two-dimensional (2D) culture. In this study, we found that bone marrow derived mesenchymal stem cells (BMSCs) cultured in 3D collagen scaffold (3D BMSCs) exhibited distinctive features including significantly enhancing neurotrophic factor secretions and reducing macrophage activations challenged by lipopolysaccharide (LPS) in vitro. To further evaluate 3D BMSCs' potential benefits to the regeneration of spinal cord injury (SCI), the 3D and 2D BMSCs were respectively implanted in rat hemisected SCI. Compared with 2D cohort, 3D BMSCs transplantation significantly reduced the expressions of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 at 5 days after transplantation, markedly enhanced axonal regeneration, and promoted motor functional recovery during 8 weeks of observation. When Nocodazole was used to depolymerize the cytoskeleton of 3D BMSCs, the changed expressions of neurotrophic factors and inflammatory cytokines were blunted, at least partially. Thus synergistic effects of neuronal protection and immunomodulation of 3D BMSCs may lead to a better functional recovery of SCI and the underlying mechanism may involve the alteration of their cellular morphology because of 3D culture. This study contributes to a better understanding of the cellular characteristics of 3D BMSCs and provides a novel strategy to promote the repair of the injured spinal cord. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1759-1769, 2016.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Han
authors.affiliation: Regeneration Medical Center, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.|Graduate School, Chinese Academy of Sciences, Beijing, 100080, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Public Health of Agricultural Ministry, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods*; D048430:Cell Shape; D003094:Collagen / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D056747:Immunomodulation / Q000187:drug effects*; D007249:Inflammation / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015739:Nocodazole / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D003094:Collagen; D015739:Nocodazole
keywords: bone marrow derived mesenchymal stem cells; inflammatory cytokines; neurotrophic factors; spinal cord injury; three-dimensional culture