Zhang Shuning, Ma Xin, Yao Kang, Zhu Hong, Huang Zheyong, Shen Li, Qian Juying, Zou Yunzeng, Sun Aijun, Ge Junbo
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
J Cell Mol Med. 2014 Jun;18(6):1236-8. doi: 10.1111/jcmm.12301. Epub 2014 Jun 19.
Detection of the optimal cell transplantation strategy for myocardial infarction (MI) has attracted a great deal of attention. Commitment of engrafted cells to angiogenesis within damaged myocardium is regarded as one of the major targets in cell-based cardiac repair. Bone marrow-derived CD34-positive cells, a well-characterized population of stem cells, might represent highly functional endothelial progenitor cells and result in the formation of new blood vessels. Recently, physical microenvironment (extracellular matrix stiffness) around the engrafted cells was found to exert an essential impact on their fate. Stem cells are able to feel and respond to the tissue-like matrix stiffness to commit to a relevant lineage. Notably, the infarct area after MI experiences a time-dependent stiffness change from flexible to rigid. Our previous observations demonstrated myocardial stiffness-dependent differentiation of the unselected bone marrow-derived mononuclear cells (BMMNCs) along endothelial lineage cells. Myocardial stiffness (~42 kPa) within the optimal time domain of cell engraftment (at week 1 to 2) after MI provided a more favourable physical microenvironment for cell specification and cell-based cardiac repair. However, the difference in tissue stiffness-dependent cell differentiation between the specific cell subsets expressing and no expressing CD34 phenotype remains uncertain. We presumed that CD34-positive cell subsets facilitated angiogenesis and subsequently resulted in cardiac repair under induction of infarcted myocardium-like matrix stiffness compared with CD34-negative cells. If the hypothesis were true, it would contribute greatly to detect the optimal cell subsets for cell therapy and to establish an optimized therapy strategy for cell-based cardiac repair.
心肌梗死（MI）最佳细胞移植策略的研究备受关注。植入细胞在受损心肌内促成血管生成被视为基于细胞的心脏修复的主要目标之一。骨髓来源的CD34阳性细胞是一种特征明确的干细胞群体，可能代表高功能的内皮祖细胞，并导致新血管的形成。最近发现，植入细胞周围的物理微环境（细胞外基质硬度）对其命运具有至关重要的影响。干细胞能够感知并响应组织样基质硬度，从而分化为相关谱系。值得注意的是，心肌梗死后梗死区域会经历从柔韧到僵硬的时间依赖性硬度变化。我们之前的观察表明，未分选的骨髓来源单核细胞（BMMNCs）会根据心肌硬度在内皮谱系细胞中发生分化。心肌梗死后细胞植入的最佳时域（第1至2周）内的心肌硬度（约42 kPa）为细胞定向分化和基于细胞的心脏修复提供了更有利的物理微环境。然而，表达和不表达CD34表型的特定细胞亚群之间在组织硬度依赖性细胞分化方面的差异仍不确定。我们推测，与CD34阴性细胞相比，在梗死心肌样基质硬度诱导下，CD34阳性细胞亚群促进血管生成，进而实现心脏修复。如果这一假设成立，将对检测细胞治疗的最佳细胞亚群以及建立基于细胞的心脏修复优化治疗策略有很大帮助。
