Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo

被引:391
作者
Guimaraes-Camboa, Nuno [1 ,2 ,3 ]
Cattaneo, Paola [1 ]
Sun, Yunfu [4 ]
Moore-Morris, Thomas [5 ]
Gu, Yusu [6 ]
Dalton, Nancy D. [6 ]
Rockenstein, Edward [7 ]
Masliah, Eliezer [7 ]
Peterson, Kirk L. [6 ]
Stallcup, William B. [8 ]
Chen, Ju [6 ]
Evans, Sylvia M. [1 ,6 ,9 ]
机构
[1] Univ Calif San Diego, Skaggs Sch Pharm, La Jolla, CA 92093 USA
[2] Univ Porto, Inst Biomed Sci Abel Salazar, P-4050313 Oporto, Portugal
[3] Univ Porto, GABBA Grad Program, P-4050313 Oporto, Portugal
[4] Tongji Univ, Sch Med, East Hosp, Key Lab Arrhythmia,Minist Educ, Shanghai 200120, Peoples R China
[5] Aix Marseille Univ, INSERM, UMRS 910, F-13284 Marseille, France
[6] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[7] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[8] Sanford Burnham Prebys Med Discovery Inst, Tumor Microenvironm & Canc Immunol Program, Ctr Canc, La Jolla, CA 92037 USA
[9] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
基金
中国国家自然科学基金;
关键词
SKELETAL-MUSCLE; SATELLITE CELLS; TBX18; EXPRESSION; LINEAGE; CARDIOMYOCYTES; PRECURSORS; ORIGIN; CONTRIBUTE; CONVERSION;
D O I
10.1016/j.stem.2016.12.006
中图分类号
Q813 [细胞工程];
学科分类号
100113 [医学细胞生物学];
摘要
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. Fluorescence-activated cell sorting (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.
引用
收藏
页码:345 / +
页数:20
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