title: Combined Use of Mesenchymal Stromal Cell Sheet Transplantation and Local Injection of SDF-1 for Bone Repair in a Rat Nonunion Model.
abstract: Bone nonunion treatments pose a challenge in orthopedics. This study investigated the joint effects of using mesenchymal stem cell (MSC) sheets with local injection of stromal cell-derived factor-1 (SDF-1) on bone formation. In vitro, we found that migration of MSCs was mediated by SDF-1 in a dose-dependent manner. Moreover, stimulation with SDF-1 had no direct effect on the proliferation or osteogenic differentiation of MSCs. Furthermore, the results indicated elevated expression levels of bone morphogenetic protein 2, alkaline phosphatase, osteocalcin, and vascular endothelial growth factor in MSC sheets compared with MSCs cultured in medium. New bone formation in fractures was evaluated by X-ray, micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, Safranin-O staining, and immunohistochemistry in vivo. In the rat bone fracture model, the MSC sheets transplanted into the injured site along with injection of SDF-1 showed significantly more new bone formation within the gap. Moreover, at 8 weeks, complete bone union was obtained in this group. In contrast, the control group showed nonunion of the bone. Our study suggests a new strategy involving the use of MSC sheets with a local injection of SDF-1 for hard tissue reconstruction, such as the healing of nonunions and bone defects.
authors.affiliation: Department of Orthopedic Surgery, Minhang Hospital, Fudan University, Shanghai, P.R. China.|Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Guangnan
authors.initials: G
authors.lastname: Chen
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Shanghai Medical School of Fudan University, Shanghai, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Fang
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Orthopedic Surgery, Minhang Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Tuoyu
authors.initials: T
authors.lastname: Di
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.|Department of Orthopaedic Surgery, Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, P.R. China.|Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital, Hangzhou, P.R. China.|Institute of Orthopaedics and Traumatology of Zhejiang Province, Hangzhou, P.R. China.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D050723:Fractures, Bone / Q000473:pathology / Q000628:therapy* / Q000662:veterinary; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D059467:Transcriptome / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D054377:Chemokine CXCL12; D042461:Vascular Endothelial Growth Factor A; D015675:Osteocalcin; D000469:Alkaline Phosphatase
keywords: Fracture; Mesenchymal stem cell (MSC) sheet; Mesenchymal stem cells (MSCs); Stromal cell-derived factor (SDF)