Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan 30013, ROC.
Biomaterials. 2011 Aug;32(24):5558-67. doi: 10.1016/j.biomaterials.2011.04.031. Epub 2011 May 8.
Stem cell transplantation may repair the infarcted heart. Despite the encouraging preliminary results, an optimal cell type used and low retention of the transplanted cells remain to be overcome. In this study, a multiwelled methylcellulose hydrogel system was used to cultivate human amniotic-fluid stem cells (hAFSCs) to form spherically symmetric cell bodies for cellular cardiomyoplasty. The grown hAFSC bodies enriched with extracellular matrices (ECM) were xenogenically transplanted in the peri-infarct area of an immune-suppressed rat, via direct intramyocardial injection. Results of bioluminescence imaging and real-time PCR revealed that hAFSC bodies could considerably enhance cell retention and engraftment in short-term and long-term observations, when compared with dissociated hAFSCs. Echocardiography and magnetic resonance imaging showed that the enhanced cell engraftment in the hAFSC-body group could significantly attenuate the progression of heart failure, improve the global function, and increase the regional wall motion. At the infarct, expressions of HGF, bFGF and VEGF were significantly up-regulated, an indication of the significantly increased vessel densities in the hearts treated with hAFSC bodies. The injected hAFSC bodies could undergo differentiation into angiogenic and cardiomyogenic lineages and contribute to functional benefits by direct regeneration. The aforementioned results demonstrate that hAFSC bodies can attenuate cell loss after intramuscular injection by providing an adequate physical size and offering an enriched ECM environment to retain the transplanted cells in the myocardium, thus improving heart function.
干细胞移植可能修复梗死的心脏。尽管初步结果令人鼓舞，但仍需要克服最佳细胞类型的使用和移植细胞的低保留率。在这项研究中，使用多室甲基纤维素水凝胶系统培养人羊水干细胞（hAFSCs）以形成球对称的细胞体，用于细胞心肌成形术。富含细胞外基质（ECM）的生长 hAFSC 体通过直接心肌内注射异种移植到免疫抑制大鼠的梗死周围区域。生物发光成像和实时 PCR 的结果表明，与分离的 hAFSCs 相比，hAFSC 体可以在短期和长期观察中显著提高细胞保留和植入率。超声心动图和磁共振成像显示，hAFSC 体组中增强的细胞植入可以显著减轻心力衰竭的进展，改善整体功能，并增加局部壁运动。在梗死区，HGF、bFGF 和 VEGF 的表达明显上调，表明用 hAFSC 体处理的心脏中血管密度明显增加。注射的 hAFSC 体可以分化为血管生成和心肌生成谱系，并通过直接再生为心脏功能带来益处。上述结果表明，hAFSC 体可以通过提供足够的物理大小并为移植细胞提供富含细胞外基质的环境来保留在心肌中，从而减轻肌肉内注射后的细胞丢失，从而改善心脏功能。
