Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo.
Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo.
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DOI：
10.1016/j.stem.2016.12.006
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发表时间：
2017-03-02
期刊：
影响因子：
23.9
通讯作者：
Evans SM
中科院分区：
文献类型：
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作者：
Guimarães-Camboa N;Cattaneo P;Sun Y;Moore-Morris T;Gu Y;Dalton ND;Rockenstein E;Masliah E;Peterson KL;Stallcup WB;Chen J;Evans SM
周细胞被广泛认为是间充质干细胞（MSC）-多能组织驻留祖细胞，具有再生医学的巨大潜力。从不同组织分离的培养的周细胞可以在体外或在体内移植后分化成多种细胞类型。然而，内源性周细胞在体内的细胞命运可塑性仍不清楚。在这里，我们表明，转录因子Tbx 18选择性标记周细胞和血管平滑肌细胞在成年小鼠的多个器官。FACS纯化的Tbx 18表达细胞在体外表现为MSC。然而，使用诱导型Tbx 18-CreERT 2系的谱系追踪实验显示，周细胞和血管平滑肌细胞在衰老和不同的病理环境中保持其身份，并且对其他细胞谱系没有显着贡献。这些结果挑战了目前认为内源性周细胞是多能组织驻留祖细胞的观点，并表明在体外或体内移植后观察到的可塑性来自体外人工细胞操作。Guimares-Camboa等人在体内永久标记了多个器官的周细胞和血管平滑肌，并跟踪了这些细胞在衰老和损伤模型中的命运。他们的分析表明，在体内，周细胞不表现为干细胞，挑战了目前周细胞作为组织驻留多能祖细胞的观点。
Pericytes are widely believed to function as mesenchymal stem cells (MSCs) -multipotent tissue-resident progenitors with great potential for regenerative medicine. Cultured pericytes isolated from distinct tissues can differentiate into multiple cell types in vitro, or following transplantation in vivo. However, the cell fate plasticity of endogenous pericytes in vivo remains unclear. Here, we show that the transcription factor Tbx18 selectively marks pericytes and vascular smooth muscle cells in multiple organs of adult mouse. FACS-purified Tbx18-expressing cells behaved as MSCs in vitro. However, lineage-tracing experiments using an inducible Tbx18-CreERT2 line revealed that pericytes and vascular smooth muscle cells maintained their identity in aging and diverse pathological settings, and did not significantly contribute to other cell lineages. These results challenge the current view of endogenous pericytes as multipotent tissue-resident progenitors, and suggest that the plasticity observed in vitro or following transplantation in vivo arises from artificial cell manipulations ex vivo. Guimarães-Camboa et al. permanently labeled pericytes and vascular smooth muscle of multiple organs in vivo and followed the fate of these cells in aging and injury models. Their analyses showed that, in vivo, pericytes did not behave as stem cells, challenging the current view of pericytes as tissue-resident multipotent progenitors.