Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC; Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
J Control Release. 2013 Dec 10;172(2):419-25. doi: 10.1016/j.jconrel.2013.06.025. Epub 2013 Jul 1.
Cell-based therapeutic neovascularization is a promising method for treating ischemic disorders. In this work, human umbilical vein endothelial cells (HUVECs) were thoroughly premixed with cord-blood mesenchymal stem cells (cbMSCs) and cultivated to form three-dimensional (3D) cell aggregates for cellular cardiomyoplasty. In the in vitro study, tubular networks were formed at day 1 after the co-culturing of dissociated HUVECs and cbMSCs on Matrigel; however, as time progressed, the grown tubular networks regressed severely. Conversely, when 3D cell aggregates were grown on Matrigel, mature and stable tubular networks were observed over time, under the influence of their intensive cell-extracellular matrix (ECM) interactions and cell-cell contacts. 3D cell aggregates were transplanted into the peri-infarct zones of rats with myocardial infarction (MI) via direct intramyocardial injection. Based on our pinhole single photon emission computed tomography (SPECT) myocardial-perfusion observations, echocardiographic heart-function examinations and histological analyses, the engrafted 3D cell aggregates considerably enhanced the vascular densities and the blood flow recovery in the ischemic myocardium over those of their dissociated counterparts, thereby reducing the size of perfusion defects and restoring cardiac function. These results demonstrate that the intramuscular delivery of 3D cell aggregates of HUVECs/cbMSCs can be a valuable cell-based regenerative therapeutic strategy against MI.
基于细胞的治疗性血管新生是治疗缺血性疾病的一种很有前途的方法。在这项工作中，将人脐静脉内皮细胞（HUVEC）与脐血间充质干细胞（cbMSC）充分预混，并培养形成三维（3D）细胞聚集体进行细胞心肌成形术。在体外研究中，将分离的 HUVEC 和 cbMSC 在 Matrigel 上共培养 1 天后形成管状网络；然而，随着时间的推移，生长的管状网络严重退化。相反，当 3D 细胞聚集体在 Matrigel 上生长时，在其密集的细胞-细胞外基质（ECM）相互作用和细胞-细胞接触的影响下，随着时间的推移观察到成熟和稳定的管状网络。将 3D 细胞聚集体通过直接心肌内注射移植到心肌梗死（MI）大鼠的梗死周围区。基于我们的小孔单光子发射计算机断层扫描（SPECT）心肌灌注观察、超声心动图心功能检查和组织学分析，与分离的细胞相比，移植的 3D 细胞聚集体显著增加了缺血心肌中的血管密度和血流恢复，从而减少了灌注缺陷的大小并恢复了心脏功能。这些结果表明，HUVEC/cbMSC 的 3D 细胞聚集体的肌内递送可能是一种针对 MI 的有价值的基于细胞的再生治疗策略。
