近日，美国贝勒医学院Dongsu Park研究团队的一项工作鉴定了功能不同的Mx1/αSMA双阳性骨膜骨骼干细胞。2019年12月5日出版的《细胞—干细胞》发表了这项成果。

研究人员发现，动物模型可以选择性地、持久地标记产后Mx1⁺αSMA⁺骨膜干细胞（P-SSC），并确定P-SSC是长期繁殖的、功能独特的SSC亚群，负责终身生成骨膜成骨细胞。P-SSC迅速向损伤部位迁移，提供成骨细胞和软骨细胞，并恢复新的骨膜。

值得注意的是，P-SSC特异性表达CCL5受体CCR3和CCR5。实时活体成像显示，使用CCL5进行治疗可诱导P-SSC在体内迁移并促进骨愈合，而CCL5/CCR5缺失、CCR5抑制或局部P-SSC敲除可减少成骨细胞数量并延迟骨愈合。人骨膜细胞表达CCR5并经历CCL5介导的迁移。因此，成年骨膜通过骨骼维护和损伤修复所需的CCL5依赖性迁移机制维持遗传上不同的SSC亚群。

据了解，骨膜对于骨骼的维持和愈合至关重要。然而，成年骨膜驻留骨骼干细胞的体内身份和特定的调节机制尚不清楚。

附：英文原文

Title: Identification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells

Author: Laura C. Ortinau, Hamilton Wang, Kevin Lei, Lorenzo Deveza, Youngjae Jeong, Yannis Hara, Ingo Grafe, Scott B. Rosenfeld, Dongjun Lee, Brendan Lee, David T. Scadden, Dongsu Park

Issue&Volume: 2019/12/05

Abstract: The periosteum is critical for bone maintenance and healing. However, the in vivo identity and specific regulatory mechanisms of adult periosteum-resident skeletalstem cells are unknown. Here, we report animal models that selectively and durablylabel postnatal Mx1+αSMA+ periosteal stem cells (P-SSCs) and establish that P-SSCs are a long-term repopulating,functionally distinct SSC subset responsible for lifelong generation of periostealosteoblasts. P-SSCs rapidly migrate toward an injury site, supply osteoblasts andchondrocytes, and recover new periosteum. Notably, P-SSCs specifically express CCL5receptors, CCR3 and CCR5. Real-time intravital imaging revealed that the treatmentwith CCL5 induces P-SSC migration in vivo and bone healing, while CCL5/CCR5 deletion, CCR5 inhibition, or local P-SSC ablationreduces osteoblast number and delays bone healing. Human periosteal cells expressCCR5 and undergo CCL5-mediated migration. Thus, the adult periosteum maintains geneticallydistinct SSC subsets with a CCL5-dependent migratory mechanism required for bone maintenanceand injury repair.

DOI: 10.1016/j.stem.2019.11.003

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30458-8