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首页> 外文期刊>FEBS Open Bio >Coculture of endothelial progenitor cells and mesenchymal stem cells enhanced their proliferation and angiogenesis through PDGF and Notch signaling
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Coculture of endothelial progenitor cells and mesenchymal stem cells enhanced their proliferation and angiogenesis through PDGF and Notch signaling

机译：内皮祖细胞和间充质干细胞的共培养通过PDGF和Notch信号增强了它们的增殖和血管生成

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The beneficial effects of combined use of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) on tissue repair and regeneration after injury have been demonstrated, but the underlying mechanism remains incompletely understood. This study aimed to investigate the effects of direct contact coculture of human bone marrow‐derived EPCs (hEPCs)/human bone marrow‐derived MSCs (hMSCs) on their proliferation and angiogenic capacities and the underlying mechanism. hEPCs and hMSCs were cocultured in a 2D mixed monolayer or a 3D transwell membrane cell‐to‐cell coculture system. Cell proliferation was determined by Cell Counting Kit‐8. Angiogenic capacity was evaluated by in vitro angiogenesis assay. Platelet‐derived growth factor‐BB (PDGF‐BB), PDGF receptor neutralizing antibody (AB‐PDGFR), and DAPT (a γ‐secretase inhibitor) were used to investigate PDGF and Notch signaling. Cell proliferation was significantly enhanced by hEPCs/hMSCs 3D‐coculture and PDGF‐BB treatment, but inhibited by AB‐PDGFR. Expression of cyclin D1, PDGFR, Notch1, and Hes1 was markedly enhanced by PDGF‐BB but inhibited by DAPT. In vitro angiogenesis assay showed that hEPCs/hMSCs coculture and PDGF‐BB significantly enhanced angiogenic capacity, whereas AB‐PDGFR significantly reduced the angiogenic capacity. PDGF‐BB increased the expression of kinase insert domain receptor (KDR, an endothelial marker) and activated Notch1 signaling in cocultured cells, while DAPT attenuated the promoting effect of PDGF‐BB on KDR expression of hEPCs/hMSCs coculture. hEPCs/hMSCs coculture enhanced their proliferation and angiogenic capacities. PDGF and Notch signaling pathways participated in the promoting effects of hEPCs/hMSCs coculture, and there was crosstalk between these two signaling pathways. Our findings should aid understanding of the mechanism of beneficial effects of hEPCs/hMSCs coculture.
机译：间充质干细胞（MSCs）和内皮祖细胞（EPCs）联合使用对损伤后组织修复和再生的有益作用已得到证实，但其潜在机制仍未完全了解。这项研究旨在研究人骨髓来源的EPC（hEPC）/人骨髓来源的MSC（hMSC）直接接触共培养对其增殖和血管生成能力及其潜在机制的影响。 hEPC和hMSC在2D混合单层或3D Transwell膜细胞间共培养系统中共培养。细胞增殖是通过Cell Counting Kit-8确定的。通过体外血管生成测定法评估血管生成能力。血小板衍生生长因子-BB（PDGF-BB），PDGF受体中和抗体（AB-PDGFR）和DAPT（一种γ-分泌酶抑制剂）被用于研究PDGF和Notch信号传导。 hEPCs / hMSCs 3D共培养和PDGF-BB处理可显着增强细胞增殖，但AB-PDGFR可抑制细胞增殖。 PDGF-BB显着增强了细胞周期蛋白D1，PDGFR，Notch1和Hes1的表达，但被DAPT抑制。体外血管生成测定表明，hEPC / hMSCs共培养和PDGF-BB显着增强了血管生成能力，而AB-PDGFR显着降低了血管生成能力。 PDGF-BB在共培养的细胞中增加了激酶插入域受体（KDR，一种内皮标记）的表达并激活了Notch1信号传导，而DAPT减弱了PDGF-BB对hEPC / hMSCs共培养的KDR表达的促进作用。 hEPCs / hMSCs共培养可增强其增殖和血管生成能力。 PDGF和Notch信号通路参与了hEPC / hMSCs共培养的促进作用，这两个信号通路之间存在串扰。我们的发现应有助于了解hEPC / hMSCs共培养的有益作用机理。

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