Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction.
Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction.
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DOI：
10.1016/j.biomaterials.2010.10.005
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发表时间：
2011-03
期刊：
影响因子：
14
通讯作者：
Hubbell JA
中科院分区：
文献类型：
--
作者：
Kraehenbuehl TP;Ferreira LS;Hayward AM;Nahrendorf M;van der Vlies AJ;Vasile E;Weissleder R;Langer R;Hubbell JA
我们报道了一种人工合成的、可注射的基质金属蛋白酶反应的生物活性水凝胶作为原位形成的支架，将胸腺素β4(Tβ4)与来自人胚胎干细胞的血管细胞一起输送到大鼠心脏缺血性损伤中。胸腺素F4是一种促血管生成和促进生存的因子。发现该凝胶可替代大鼠梗死心肌中降解的细胞外基质，促进天然内皮细胞的结构组织，而部分输送的hESC来源的血管细胞在梗死区形成新生毛细血管。磁共振成像显示，与对照组(3d射血分数，+~7%，P<；0.001；6wk射血分数，+~12%，P<；0.001)相比，微血管移植有效地保持了心肌梗死后3d和6wk的收缩性能，减轻了左室扩张，缩小了梗塞面积。治疗后观察到血管密度的升高，这可能部分是由于人类(供体)衍生的细胞因子EGF、VEGF和HGF(1d)的升高所致。因此，用于血管细胞和药物双重输送的临床相关基质可能在工程持续组织保存和潜在的再生缺血心肌组织中有用。
We present use of a synthetic, injectable matrix-metalloproteinase (MMP)- responsive, bioactive hydrogel as an in situ forming scaffold to deliver thymosin β4 (Tβ4), a pro-angiogenic and pro-survival factor, along with vascular cells derived from human embryonic stem cells (hESC) in ischemic injuries to the heart in a rat model. The gel was found to substitute the degrading extracellular matrix in the infarcted myocardium of rats and to promote structural organization of native endothelial cells, while some of the delivered hESC-derived vascular cells formed de novo capillaries in the infarct zone. Magnetic resonance imaging (MRI) revealed that the microvascular grafts effectively preserved contractile performance 3 d and 6 wk after myocardial infarction, attenuated left ventricular dilation, and decreased infarct size as compared to infarcted rats treated with PBS injection as a control (3 d ejection fraction, + ~7%, P<0.001; 6 wk ejection faction, + ~12%, P<0.001). Elevation in vessel density was observed in response to treatment, which may be due in part to elevations in human (donor)-derived cytokines EGF, VEGF and HGF (1 d). Thus, a clinically relevant matrix for dual delivery of vascular cells and drugs may be useful in engineering sustained tissue preservation and potentially regenerating ischemic cardiac tissue.
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