Reconstitute the damaged heart via the dual reparative roles of pericardial adipose-derived flk-1+ stem cells
Reconstitute the damaged heart via the dual reparative roles of pericardial adipose-derived flk-1+ stem cells
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通过心包脂肪来源的 flk-1 干细胞的双重修复作用重建受损心脏
DOI：
10.1016/j.ijcard.2015.09.002
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Zhaoping Ding
中科院分区：
文献类型：
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作者：
Xiaoming Wang;Xueqing Liu;Hui Zhang;Liangming Nie;Min Chen;Zhaoping Ding
背景技术背景：心包脂肪来源的基质细胞（pADSC）具有“第二心脏区域”的发育起源，因此有利于肌源性分化。本实验通过定义标记有flk-1（VEGF的II型受体）表达的pADSC的子集来扩展我们先前的观察，flk-1是VEGF的II型受体以有效地增强心脏修复。方法和结果：免疫荧光和流式细胞术显示，flk-1阳性细胞在心包组织和总分离的pADSC中约占12%。经磁分选纯化的flk-1阳性pADSC（flk-1 pospADSC）在培养过程中可形成球形结构，同时产生肌源性前体（cTnT+）和血管源性前体（vWF+）。在心肌内移植到缺血心脏后，flk-1 pospADSC产生了比PBS对照或flk-1 pospADSC更上级的结构修复，其特征在于梗塞壁的增厚，其中显著确保了微血管的肌生成和血管生成（优选varphi<50 μ m）（p<0.01）。移植后28天，结构受益也转化为功能恢复（EF=44% vs. 62%，p<0.01）。进一步用BrdU进行脉冲追踪标记实验，发现新肌生成和新血管生成有助于结构修复。新形成的心肌是由于先前存在的心肌细胞增殖重新进入细胞周期（ki-67阳性）。结论：Flk-1 pospADSC在体外能够同时产生肌源性和血管源性前体细胞，并且在体内移植后，通过微血管和心肌细胞的新形成来重建受损的心脏，因此代表了用于基于干细胞的治疗的有吸引力的供体细胞
BACKGROUND: The pericardial adipose derived stromal cells (pADSC) own a developmental origin from the "second heart field" and thus favor myogenic differentiation. The present experiments extended our previous observation by defining a subset of pADSC marked with the expression of flk-1, a type II receptor for VEGF to efficiently enhance cardiac repair. METHODS AND RESULTS: Immunofluorescence and flow cytometry showed that flk-1 positive cells represented about 12% in the pericardial tissue and the total isolated pADSC. The purified flk-1 positive pADSC by magnetic sorting (flk-1pospADSC) show the ability of forming spherical structure in which both myogenic (cTnT+) and angiogenic (vWF+) precursors were concurrently generated in culture. After being intramyocardially transplanted into the ischemic hearts, flk-1pospADSC yielded superior structural repair to PBS control or flk-1negpADSC, characterized by the thickening of the infarcted wall in which both myogenesis and angiogenesis of microvasculature (preferentially with varphi<50 mum) were significantly ensured (p<0.01). The structure benefits were also translated into a functional restoration 28 days after transplantation (EF=44% vs. 62%, p<0.01). Further pulse-chase labeling experiments with BrdU revealed that neomyogenesis and neoangiogenesis contribute in the structural repair. The newly formed myocardium was resulted from the proliferation of pre-existing cardiomyocytes that re-entered cell cycle (ki-67 positive). CONCLUSION: Flk-1pospADSC are capable of concurrently giving rise to both myogenic and angiogenic precursors in vitro and, after transplantation in vivo, to reconstitute the damaged heart by the neoformation of microvasculature and of cardiomyocytes and thus represent an attracting donor cells for stem cell-based therapy