title: Promotion of neurological recovery in rat spinal cord injury by mesenchymal stem cells loaded on nerve-guided collagen scaffold through increasing alternatively activated macrophage polarization.
abstract: Mesenchymal stem cells (MSCs) are characterized by multidifferentiation and immunoregulatory potential and have been used in the treatment of spinal cord injury (SCI), but direct transplantation may limit effectiveness due to their quick diffusion. The role of macrophages in healing is being increasingly recognized because of their ability to polarize into pro- and anti-inflammatory phenotypes. In the present study, nerve-guide collagen scaffold (CS) combined with rat MSCs was developed. After CS was confirmed to minimize MSC distribution in vivo by positron emission tomography (PET) imaging, the repair capacity of combined implantation of CS and MSCs and the effect on classically activated macrophage/alternatively activated macrophage (M2) polarization was assessed in a hemisected SCI rat model. In vivo studies showed that, compared to the control group, the rats in the combined implantation group exhibited more significant recovery of nerve function evidenced by the 21-point Basso-Beattie-Bresnahan score and footprint analysis. Morphological staining showed less macrophage infiltration, apoptosis and glial fibrillary acidic protein, and more neurofilaments, and the fibres were guided to grow through the implant. More M2 were observed in the combined implantation group. The data suggest that the combined implantation could support MSCs to play a protective role of SCI, not only through inhibiting chronic scar formation and providing linear guidance for the nerve, but also benefitting M2 polarization to form an anti-inflammatory environment. Thus, the combination of biomaterial and MSCs might be a prominent therapeutic treatment for SCI. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Soochow University. Orthopedic Institute, Soochow University, Suzhou, P.R. China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Soochow University. Orthopedic Institute, Soochow University, Suzhou, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Soochow University. Orthopedic Institute, Soochow University, Suzhou, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yue
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Soochow University. Orthopedic Institute, Soochow University, Suzhou, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Soochow University. Orthopedic Institute, Soochow University, Suzhou, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Soochow University. Orthopedic Institute, Soochow University, Suzhou, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Soochow University. Orthopedic Institute, Soochow University, Suzhou, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D002417:Cattle; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D009043:Motor Activity / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016019:Survival Analysis; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D015703:Antigens, CD; D005904:Glial Fibrillary Acidic Protein; D019788:Fluorodeoxyglucose F18; D003094:Collagen; D052247:Nitric Oxide Synthase Type II
keywords: alternatively activated macrophage; classically activated macrophage; collagen scaffold; mesenchymal stem cells; neurological recovery; spinal cord injury