Badawi Amrilmaen, Jefferson Osfred C, Huuskes Brooke M, Ricardo Sharon D, Kerr Peter G, Samuel Chrishan S, Murthi Padma
Cardiovascular Disease Program, Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia.
Centre for Cardiovascular Biology and Disease Research, Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Melbourne, VIC 3086, Australia.
Biomedicines. 2022 Apr 12;10(4):883. doi: 10.3390/biomedicines10040883.
Circulating bone marrow-derived endothelial progenitor cells (EPCs) facilitate vascular repair in several organs including the kidney but are progressively diminished in end-stage kidney disease (ESKD) patients, which correlates with cardiovascular outcomes and related mortality. We thus determined if enhancing the tissue-reparative effects of human bone marrow-derived mesenchymal stromal cells (BM-MSCs) with the vasculogenic effects of recombinant human relaxin (RLX) could promote EPC proliferation and function. CD34 EPCs were isolated from the blood of healthy and ESKD patients, cultured until late EPCs had formed, then stimulated with BM-MSC-derived condition media (CM; 25%), RLX (1 or 10 ng/mL), or both treatments combined. Whilst RLX alone stimulated EPC proliferation, capillary tube formation and wound healing in vitro, these measures were more rapidly and markedly enhanced by the combined effects of BM-MSC-derived CM and RLX in EPCs derived from both healthy and ESKD patients. These findings have important clinical implications, having identified a novel combination therapy that can restore and enhance EPC number and function in ESKD patients.
循环中的骨髓来源的内皮祖细胞（EPCs）有助于包括肾脏在内的多个器官的血管修复，但在终末期肾病（ESKD）患者中会逐渐减少，这与心血管结局及相关死亡率相关。因此，我们研究了利用重组人松弛素（RLX）的血管生成作用增强人骨髓来源的间充质基质细胞（BM-MSCs）的组织修复作用是否能促进EPC的增殖和功能。从健康人和ESKD患者的血液中分离出CD34 EPCs，培养至晚期EPCs形成，然后用BM-MSC来源的条件培养基（CM；25%）、RLX（1或10 ng/mL）或两种处理联合刺激。虽然单独使用RLX可刺激EPC在体外的增殖、毛细血管管腔形成和伤口愈合，但在健康人和ESKD患者来源的EPCs中，BM-MSC来源的CM和RLX的联合作用能更快、更显著地增强这些指标。这些发现具有重要的临床意义，确定了一种新型联合疗法，可恢复和增强ESKD患者的EPC数量及功能。
