Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity.
Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity.
复制标题
DOI：
10.1002/stem.1868
复制
发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Péault B
中科院分区：
文献类型：
--
作者：
Chen WC;Baily JE;Corselli M;Díaz ME;Sun B;Xiang G;Gray GA;Huard J;Péault B
血管周围间充质前体细胞（即周细胞）存在于骨骼肌中，在那里它们有助于肌纤维再生;然而，在心肌中存在类似的微血管相关再生前体细胞尚未被记录。我们测试了人类心肌内的微血管周细胞是否表现出与其解剖学和发育学上不同的对应物相似的表型和多能性。胎儿和成人心脏周细胞（hHP）原位表达典型的周细胞标志物，包括CD 146、NG 2、PDGFRβ、PDGFRα、αSMA和SM-MHC，但不表达CD 117、CD 133和结蛋白，也不表达内皮细胞（EC）标志物。基于阳性选择（CD 146）和阴性选择（CD 34、CD 45、CD 56和CD 117）细胞谱系标志物的组合，通过流式细胞术从心室肌中前瞻性地纯化hHP至同质。体外扩增的纯化hHP与人骨骼肌来源的周细胞（hSkMP）在表型上相似。hHP原位表达MSC标记物，并表现出骨软骨和脂肪形成潜力，但重要的是，没有骨骼肌发生的能力，与所有其他来源的周细胞不同。在基质胶培养物中，hHP支持有/无EC的网络形成; hHP进一步刺激缺氧下的血管生成反应，与hSkMP显著不同。在5-氮杂胞苷处理和新生心肌细胞体外共培养以及体内心肌内移植后，检查hHPs的心肌发生潜力。结果表明，心肌细胞分化的一小部分的hHP。总之，人类心肌周细胞与其骨骼肌同源物具有某些表型和发育相似性，但表现出不同的抗原性，肌原性和血管生成特性。这是周细胞作为天然间充质干细胞的发育潜力的解剖学限制的第一个例子。
Perivascular mesenchymal precursor cells (i.e. pericytes) reside in skeletal muscle where they contribute to myofiber regeneration; however, the existence of similar microvessel-associated regenerative precursor cells in cardiac muscle has not yet been documented. We tested whether microvascular pericytes within human myocardium exhibit phenotypes and multipotency similar to their anatomically and developmentally distinct counterparts. Fetal and adult human heart pericytes (hHPs) express canonical pericyte markers in situ, including CD146, NG2, PDGFRβ, PDGFRα, αSMA, and SM-MHC, but not CD117, CD133 and desmin, nor endothelial cell (EC) markers. hHPs were prospectively purified to homogeneity from ventricular myocardium by flow cytometry, based on a combination of positive- (CD146) and negative-selection (CD34, CD45, CD56, and CD117) cell lineage markers. Purified hHPs expanded in vitro were phenotypically similar to human skeletal muscle-derived pericytes (hSkMPs). hHPs express MSC markers in situ and exhibited osteo- chondro-, and adipogenic potentials but, importantly, no ability for skeletal myogenesis, diverging from pericytes of all other origins. hHPs supported network formation with/without ECs in Matrigel cultures; hHPs further stimulated angiogenic responses under hypoxia, markedly different from hSkMPs. The cardiomyogenic potential of hHPs was examined following 5-azacytidine treatment and neonatal cardiomyocyte co-culture in vitro, and intramyocardial transplantation in vivo. Results indicated cardiomyocytic differentiation in a small fraction of hHPs. In conclusion, human myocardial pericytes share certain phenotypic and developmental similarities with their skeletal muscle homologs, yet exhibit different antigenic, myogenic, and angiogenic properties. This is the first example of an anatomical restriction in the developmental potential of pericytes as native mesenchymal stem cells.