Aix Marseille Univ, INSERM 1263, INRA 1260, C2VN, Marseille, France.
CERIMED (European Center of Research in Medical Imaging), Aix-Marseille University, Marseille, France.
Sci Rep. 2018 Jun 20;8(1):9387. doi: 10.1038/s41598-018-27715-4.
Cell-based therapies constitute a real hope for the treatment of ischaemic diseases. One of the sources of endothelial progenitors for autologous cell therapy is Endothelial Colony Forming Cells (ECFC) that can be isolated from peripheral blood. However, their use is limited by their low number in the bloodstream and the loss of their stem cell phenotype associated with the acquisition of a senescent phenotype in culture. We hypothesized that adding soluble CD146, a novel endothelial growth factor with angiogenic properties, during the isolation and growth procedures could improve their number and therapeutic potential. Soluble CD146 increased the number of isolated peripheral blood ECFC colonies and lowered their onset time. It prevented cellular senescence, induced a partial mesenchymal phenotype and maintained a stem cell phenotype by stimulating the expression of embryonic transcription factors. These different effects were mediated through the induction of mature miR-21. When injected in an animal model of hindlimb ischaemia, sCD146-primed ECFC isolated from 40 ml of blood from patients with peripheral arterial disease were able to generate new blood vessels and restore blood flow. Treatment with sCD146 could thus constitute a promising strategy to improve the use of autologous cells for the treatment of ischaemic diseases.
细胞疗法为缺血性疾病的治疗带来了新的希望。用于自体细胞治疗的内皮祖细胞来源之一是内皮细胞集落形成细胞（ECFC），可从外周血中分离得到。然而，由于其在血液中的数量较少，以及在培养过程中获得衰老表型而丧失干细胞表型，其应用受到限制。我们假设在分离和培养过程中添加具有血管生成特性的新型内皮生长因子可溶性 CD146，可提高其数量和治疗潜能。可溶性 CD146 增加了外周血 ECFC 集落的数量，并降低了其出现时间。它通过刺激胚胎转录因子的表达，预防细胞衰老，诱导部分间充质表型，并维持干细胞表型。这些不同的作用是通过诱导成熟 miR-21 介导的。当将其注射到肢体缺血动物模型中时，从外周动脉疾病患者的 40ml 血液中分离出的经 sCD146 预处理的 ECFC 能够生成新的血管并恢复血流。因此，sCD146 的治疗可能是改善自体细胞治疗缺血性疾病的一种有前途的策略。
