间充质干细胞
脂肪组织
祖细胞
干细胞
组织工程
干细胞移植修复关节软骨
间质细胞
骨髓
脂肪生成
成体干细胞
细胞生物学
细胞分化
免疫学
癌症研究
生物
内分泌学
生物化学
遗传学
基因
作者
Yannian Gou,Yanran Huang,Wei Luo,Yanan Li,Piao Zhao,Jiamin Zhong,Xiangyu Dong,Meichun Guo,Aohua Li,Ailing Hao,Guozhi Zhao,Yonghui Wang,Ye Zhu,Hui Zhang,Yufang Shi,William Wagstaff,Hue H. Luu,Lewis L. Shi,Russell R. Reid,Tong‐Chuan He,Jiaming Fan
标识
DOI:10.1016/j.bioactmat.2023.12.003
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.
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