Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Thrombosis and Hemostasis Key Laboratory, Ministry of Education Engineering Center for Hematological Disease, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China.
J Cell Mol Med. 2017 Oct;21(10):2432-2440. doi: 10.1111/jcmm.13165. Epub 2017 May 19.
Over the past decade, cell therapies have provided promising strategies for the treatment of ischaemic cardiomyopathy. Particularly, the beneficial effects of stem cells, including bone marrow stem cells (BMSCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), have been demonstrated by substantial preclinical and clinical studies. Nevertheless stem cell therapy is not always safe and effective. Hence, there is an urgent need for alternative sources of cells to promote cardiac regeneration. Human villous trophoblasts (HVTs) play key roles in embryonic implantation and placentation. In this study, we show that HVTs can promote tube formation of human umbilical vein endothelial cells (HUVECs) on Matrigel and enhance the resistance of neonatal rat cardiomyocytes (NRCMs) to oxidative stress in vitro. Delivery of HVTs to ischaemic area of heart preserved cardiac function and reduced fibrosis in a mouse model of acute myocardial infarction (AMI). Histological analysis revealed that transplantation of HVTs promoted angiogenesis in AMI mouse hearts. In addition, our data indicate that HVTs exert their therapeutic benefit through paracrine mechanisms. Meanwhile, injection of HVTs to mouse hearts did not elicit severe immune response. Taken together, our study demonstrates HVT may be used as a source for cell therapy or a tool to study cell-derived soluble factors for AMI treatment.
在过去的十年中，细胞疗法为治疗缺血性心肌病提供了有前景的策略。特别是，大量的临床前和临床研究已经证明了干细胞（包括骨髓干细胞[BMSCs]、内皮祖细胞[EPCs]、间充质干细胞[MSCs]、胚胎干细胞[ESCs]和诱导多能干细胞[iPSCs]）的有益作用。然而，干细胞疗法并不总是安全有效的。因此，迫切需要替代细胞来源以促进心脏再生。人绒毛滋养层细胞（HVTs）在胚胎着床和胎盘形成中发挥关键作用。在这项研究中，我们表明 HVTs 可以促进人脐静脉内皮细胞（HUVECs）在 Matrigel 上的管形成，并增强新生大鼠心肌细胞（NRCMs）在体外对氧化应激的抵抗力。将 HVTs 递送到心脏缺血区域可在急性心肌梗死（AMI）小鼠模型中保存心脏功能并减少纤维化。组织学分析表明，HVTs 的移植促进了 AMI 小鼠心脏的血管生成。此外，我们的数据表明，HVTs 通过旁分泌机制发挥其治疗益处。同时，将 HVTs 注射到小鼠心脏中不会引起严重的免疫反应。总之，我们的研究表明 HVT 可用于细胞治疗或用于研究细胞衍生的可溶性因子以治疗 AMI。
