Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
Biomaterials. 2012 Jun;33(16):4069-77. doi: 10.1016/j.biomaterials.2012.02.024. Epub 2012 Mar 3.
Cellular cardiomyoplasty has been limited by poor graft retention after cell transplantation. To ensure good retention of the engrafted cells, a microfluidic device was used to fabricate spherical porous beads of poly(D,L-lactic-co-glycolic acid) as a platform for cell delivery. The beads thus obtained had a relatively uniform size, a highly porous structure, and a favorably interconnected interior architecture, to facilitate the transportation of oxygen and nutrients. These porous beads were loaded with human amniotic fluid stem cells (hAFSCs) to generate cellularized microscaffolds. Live/dead assay demonstrated that most of the cells in the porous constructs were viable. The hAFSCs that were grown in beads formed a complex three-dimensional organization with well-preserved extracellular matrices (ECM) according to their porous structure. Retention of the administered beads was clearly identified at the site of engraftment following an experimentally induced myocardial infarction in a rat model. The results of echocardiography, magnetic resonance imaging, and histological analyses suggest that the transplantation of hAFSC beads into an infarcted heart could effectively maintain its gross morphology, prevent successive ventricular expansion, and thereby improve the post-infarcted cardiac function. Immunofluorescent staining revealed that the microenvironment that was provided by the infarcted myocardium might offer cues for the induction of the engrafted hAFSCs into angiogenic and cardiomyogenic lineages. Our results demonstrate that the cellularized beads with endogenously secreted ECM were of sufficient physical size to be entrapped in the interstitial tissues following transplantation, thereby benefiting the infarcted heart.
细胞心肌成形术由于细胞移植后移植物保留效果不佳而受到限制。为确保移植细胞的良好保留，使用微流控设备制造聚（D，L-乳酸-共-乙醇酸）的球形多孔珠作为细胞输送的平台。由此获得的珠粒具有相对均匀的尺寸、高度多孔的结构和有利的相互连接的内部结构，有利于氧气和营养物质的运输。这些多孔珠被加载有人羊水干细胞（hAFSCs）以生成细胞化微支架。活/死检测表明，多孔结构中的大多数细胞都是存活的。在大鼠模型中诱导实验性心肌梗死后，在植入部位明显可以识别到已给药珠粒的保留。超声心动图、磁共振成像和组织学分析的结果表明，将 hAFSC 珠粒移植到梗死心脏中可以有效维持其大体形态，防止心室连续扩张，从而改善梗死后的心脏功能。免疫荧光染色显示，梗死心肌提供的微环境可能为植入的 hAFSCs 诱导为血管生成和心肌生成谱系提供线索。我们的结果表明，具有内部分泌型细胞外基质的细胞化珠粒具有足够的物理尺寸，可以在移植后被困在间质组织中，从而有益于梗死心脏。
