Adipose-derived mesenchymal stem cells(MSCs)are a superior cell source for bone tissue engineering  

作　　者：Yannian Gou Yanran Huang Wenping Luo Yanan Li Piao Zhao Jiamin Zhong Xiangyu Dong Meichun Guo Aohua Li Ailing Hao Guozhi Zhao Yonghui Wang Yi Zhu Hui Zhang Yunhan Shi William Wagstaff Hue H.Luu Lewis L.Shi Russell R.Reid Tong-Chuan He Jiaming Fan 

机构地区：[1]Ministry of Education Key Laboratory of Diagnostic Medicine,and Department of Clinical Biochemistry,School of Laboratory Medicine,Chongqing Medical University,Chongqing,400016,China [2]Molecular Oncology Laboratory,Department of Orthopaedic Surgery and Rehabilitation Medicine,The University of Chicago Medical Center,Chicago,IL,60637,USA [3]Departments of Orthopedic Surgery and Urology,The First Affiliated Hospital of Chongqing Medical University,Chongqing,400016,China [4]Laboratory Animal Center,Southwest University,Chongqing,400715,China [5]Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences,The Stomatological Hospital of Chongqing Medical University,Chongqing,401147,China [6]Department of Geriatrics,Xinhua Hospital,Shanghai Jiao-Tong University School of Medicine,Shanghai,200000,China [7]Department of Orthopaedic Surgery,Beijing Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100730,China [8]The Breast Cancer Center,Chongqing University Cancer Hospital,Chongqing,4000430,China [9]Department of Psychology,School of Arts and Sciences,University of Rochester,Rochester,NY,14627,USA [10]Department of Surgery,The University of Chicago Medical Center,Chicago,IL,60637,USA [11]Laboratory of Craniofacial Biology and Development,Department of Surgery Section of Plastic Surgery,The University of Chicago Medical Center,Chicago,IL,60637,USA

出　　处：《Bioactive Materials》2024年第4期51-63,共13页生物活性材料（英文）

基　　金：by research grants from the Natural Science Foundation of China(82102696 to JF);the Chongqing Bayu Young Scholar Award(JF),the 2019 Chongqing Support Program for Entrepreneurship and Innovation(No.cx2019113 to JF);the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298 to JF);the National Institutes of Health(CA226303 to TCH,and DE030480 to RRR);supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281);supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599);the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1TR002389-07.

摘　　要：Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors,osteoinductive biofactors and biocompatible scaffold materials.Mesenchymal stem cells(MSCs)represent the most promising seed cells for bone tissue engineering.As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat,MSCs can be isolated from numerous tissues and exhibit varied differentiation potential.To identify an optimal progenitor cell source for bone tissue engineering,we analyzed the proliferative activity and osteogenic potential of four commonly-used mouse MSC sources,including immortalized mouse embryonic fibroblasts(iMEF),immortalized mouse bone marrow stromal stem cells(imBMSC),immortalized mouse calvarial mesenchymal progenitors(iCAL),and immortalized mouse adipose-derived mesenchymal stem cells(iMAD).We found that iMAD exhibited highest osteogenic and adipogenic capabilities upon BMP9 stimulation in vitro,whereas iMAD and iCAL exhibited highest osteogenic capability in BMP9-induced ectopic osteogenesis and critical-sized calvarial defect repair.Transcriptomic analysis revealed that,while each MSC line regulated a distinct set of target genes upon BMP9 stimulation,all MSC lines underwent osteogenic differentiation by regulating osteogenesis-related signaling including Wnt,TGF-β,PI3K/AKT,MAPK,Hippo and JAK-STAT pathways.Collectively,our results demonstrate that adipose-derived MSCs represent optimal progenitor sources for cell-based bone tissue engineering.

关 键 词：Mesenchymal stem cell(MSC) Bone tissue engineering Multipotent progenitor cells Adipose-derived mesenchymal stem cells Osteogenic differentiation ADIPOGENESIS 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]