Department of Physiology-HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Department of Cardiothoracic Surgery and Medicine, Dunedin School of Medicine, University of Otago, New Zealand.
Cell Transplant. 2020 Jan-Dec;29:963689720972328. doi: 10.1177/0963689720972328.
Cardiovascular diseases, such as ischemic heart disease, remain the most common cause of death worldwide. Regenerative medicine with stem cell therapy is a promising tool for cardiac repair. Combination of different cell types has been shown to improve the therapeutic potential, which is thought to be due to synergistic or complimentary reparative effects. We investigated if the combination of cardiac progenitor cells (CPCs) of right atrial appendage (RAA) and left ventricle (LV) that are isolated from the same patient exert synergistic or complimentary paracrine effects for apoptotic cell death and angiogenesis in an in vitro model. Flow cytometry analysis showed that both RAA and LV CPCs expressed the mesenchymal cell markers CD90 and CD105, and were predominantly negative for the hematopoietic cell marker, CD34. Analysis of conditioned media (CM) collected from the CPCs cultured either alone or in combination in serum-deprived hypoxic conditions to simulate ischemia showed marked increase in the level of pro-survival hepatocyte growth factor and pro-angiogenic vascular endothelial growth factor-A in the combined RAA and LV CPC group. Next, to determine the therapeutic potential of CM, AC16 human ventricular cardiomyocytes and human umbilical vein endothelial cells (HUVECs) were treated with CM. Results showed a significant reduction in hypoxia-induced apoptosis of human cardiomyocytes treated with CM collected from combined RAA and LV CPC group. Similarly, matrigel assay showed a significantly increased tube length formed by HUVECs when treated with CM from combined RAA and LV CPC group. Our study provided evidence that the combination of RAA CPCs and LV CPCs may have superior therapeutic effects due to synergistic paracrine effects for cardiac repair. Therefore, in vivo studies are warranted to determine if a combination of different stem cell types have greater therapeutic potential than single-cell therapies.
心血管疾病，如缺血性心脏病，仍然是全球最常见的死亡原因。干细胞治疗的再生医学是心脏修复的有前途的工具。不同细胞类型的组合已被证明可以提高治疗潜力，这被认为是由于协同或互补的修复作用。我们研究了来自同一患者的右心房附件 (RAA) 和左心室 (LV) 的心脏祖细胞 (CPC) 的组合是否在体外模型中对凋亡细胞死亡和血管生成产生协同或互补的旁分泌作用。流式细胞术分析表明，RAA 和 LV CPC 均表达间充质细胞标记物 CD90 和 CD105，并且主要为造血细胞标记物 CD34 阴性。分析在血清剥夺缺氧条件下单独或组合培养的 CPC 收集的条件培养基 (CM) 以模拟缺血表明，联合 RAA 和 LV CPC 组中的促生存肝细胞生长因子和促血管生成血管内皮生长因子-A 的水平明显增加。接下来，为了确定 CM 的治疗潜力，用 CM 处理 AC16 人心室肌细胞和人脐静脉内皮细胞 (HUVEC)。结果表明，与单独用 CM 处理相比，用来自联合 RAA 和 LV CPC 组的 CM 处理的缺氧诱导的人心肌细胞凋亡明显减少。同样，在用来自联合 RAA 和 LV CPC 组的 CM 处理时，Matrigel 测定显示 HUVEC 形成的管长度显著增加。我们的研究提供了证据，表明由于心脏修复的协同旁分泌作用，RAA CPCs 和 LV CPCs 的组合可能具有更好的治疗效果。因此，有必要进行体内研究以确定不同干细胞类型的组合是否比单细胞疗法具有更大的治疗潜力。
