Bruce Rappaport Faculty of Medicine and Technion-Israel Institute of Technology, Haifa, Israel.
Biomaterials. 2011 Oct;32(30):7514-23. doi: 10.1016/j.biomaterials.2011.06.049. Epub 2011 Jul 23.
Myocardial cell-replacement strategies are hampered by limited sources for human cardiomyocytes and by significant cell loss following transplantation. We tested the hypothesis that a combined delivery of cardiomyocytes with an in-situ polymerizable hydrogel into a post-MI rat heart will result in better functional outcomes than each intervention alone. A photopolymerizable, biodegradable, PEGylated-fibrinogen (PF) hydrogel matrix was used as the carrier for the cardiomyocytes [neonatal rat ventricular cardiomyocytes (NRVCMs) or human embryonic stem cell-derived cardiomyocytes (hESC-CMs)]. Infarcted rat hearts (LAD ligation) were randomized to injection of saline, NRVCMs, biopolymer, or combined biopolymer-cell delivery. Echocardiography revealed typical post-infarction remodeling after 30 days in the saline-injected control group [deterioration of fractional shortening (FS) by 31.0 ± 3.6%]. Injection of NRVCMs or PF alone significantly (p < 0.01) altered this remodeling process (slightly increasing FS by 3.1 ± 6.6% and 0.5 ± 5.3% respectively). Co-injection of the NRVCMs with PF matrix resulted in a significant increase in the cell-graft area (by 144%) and in the highest improvements in FS (by 26.3 ± 6.6%). Finally, feasibility studies were performed with the PF matrix and hESC-CMs. We conclude that an injectable in-situ forming hydrogel can act as a cardiomyocyte cell-carrier and add to the beneficial effects of the grafted cells in preventing unfavorable post-infarction cardiac remodeling.
心肌细胞替代策略受到人类心肌细胞来源有限和移植后细胞大量丢失的限制。我们检验了这样一个假设，即将心肌细胞与可原位聚合的水凝胶联合递送至 MI 后大鼠心脏，将比单独干预产生更好的功能结果。一种光聚合的、可生物降解的、聚乙二醇化纤维蛋白原（PF）水凝胶基质被用作心肌细胞[新生大鼠心室心肌细胞（NRVCMs）或人胚胎干细胞衍生的心肌细胞（hESC-CMs）]的载体。梗死大鼠心脏（LAD 结扎）随机接受盐水、NRVCMs、生物聚合物或联合生物聚合物-细胞递送的注射。超声心动图显示，在生理盐水注射的对照组中，30 天后出现典型的梗死后重塑[射血分数（FS）恶化 31.0±3.6%]。单独注射 NRVCMs 或 PF 显著（p<0.01）改变了这种重塑过程（FS 分别轻微增加 3.1±6.6%和 0.5±5.3%）。NRVCMs 与 PF 基质的共同注射导致细胞移植物面积显著增加（增加 144%），FS 改善程度最高（增加 26.3±6.6%）。最后，进行了 PF 基质和 hESC-CMs 的可行性研究。我们得出结论，可注射的原位形成水凝胶可以作为心肌细胞的细胞载体，并增加移植细胞在预防梗死后心脏重塑不良方面的有益作用。
