Lahlil Rachid, Scrofani Maurice, Aries Anne, Hénon Philippe, Drénou Bernard
Institut de Recherche en Hématologie et Transplantation (IRHT), Hôpital du Hasenrain, 87 Avenue d'Altkirch, 68100 Mulhouse, France.
CellProthera, 12, rue du Parc, 68100 Mulhouse, France.
Biology (Basel). 2021 Apr 8;10(4):312. doi: 10.3390/biology10040312.
CD9 plays a crucial role in cellular growth, mobility, and signal transduction, as well as in hematological malignancy. In myeloid neoplasms, CD9 is involved in the altered interactions between leukemic and stromal cells. However, apart from its role in CD34 progenitors and myeloid and megakaryocytic differentiation, its function in normal and leukemic pluripotent cells has not yet been determined. Very small embryonic-like stem cells (VSELs) are promising pluripotent stem cells found in adult tissues that can be developed for safe and efficient regenerative medicine. VSELs express different surface receptors of the highest importance in cell functioning, including CD9, and can be effectively mobilized after organ injury or in leukemic patients. In the present study, we observed that CD9 is among the most expressed receptors in VSELs under steady-state conditions; however, once the VSELs are expanded, CD9 VSELs decrease and are more apoptotic. CD9 VSELs had no proliferative improvement in vitro compared to those that were CD9. Interestingly, the addition of SDF-1 induced CD9 expression on the surface of VSELs, as observed by flow cytometry, and improved their migration. In addition, we observed, in the phenotypically identical VSELs present in the peripheral blood of patients with myeloproliferative neoplasms, compared to healthy subjects, a significantly higher number of CD9 cells. However, in their hematopoietic stem cell (HSC) counterparts, the expression remained comparable. These results indicate that, likewise, in progenitors and mature cells, CD9 may play an important function in normal and malignant VSELs. This could explain the refractoriness observed by some groups of expanded stem cells to repairing efficiently damaged tissue when used as a source in cell therapies. Understanding the function of the CD9 receptor in normal and malignant CD34 and VSELs, along with its relationship with the CXCR4/SDF-1 pathway, will enable advances in the field of adult pluripotent cell usage in regenerative medicine and in their role in leukemia.
CD9在细胞生长、迁移和信号转导以及血液系统恶性肿瘤中发挥着关键作用。在髓系肿瘤中，CD9参与白血病细胞与基质细胞之间改变的相互作用。然而，除了其在CD34祖细胞以及髓系和巨核细胞分化中的作用外，其在正常和白血病多能细胞中的功能尚未确定。极小型胚胎样干细胞（VSELs）是在成体组织中发现的有前景的多能干细胞，可用于安全有效的再生医学。VSELs表达细胞功能中最重要的不同表面受体，包括CD9，并且在器官损伤后或白血病患者中可被有效动员。在本研究中，我们观察到在稳态条件下CD9是VSELs中表达最多的受体之一；然而，一旦VSELs被扩增，CD9+VSELs数量减少且凋亡增加。与CD9-的VSELs相比，CD9+VSELs在体外没有增殖改善。有趣的是，通过流式细胞术观察到，添加基质细胞衍生因子-1（SDF-1）可诱导VSELs表面CD9的表达，并改善其迁移。此外，我们观察到，与健康受试者相比，骨髓增殖性肿瘤患者外周血中表型相同的VSELs中，CD9+细胞数量显著更高。然而，在其造血干细胞（HSC）对应物中，表达仍相当。这些结果表明，同样在祖细胞和成熟细胞中，CD9可能在正常和恶性VSELs中发挥重要功能。这可以解释一些研究组在将扩增的干细胞用作细胞治疗来源时观察到的其难以有效修复受损组织的现象。了解CD9受体在正常和恶性CD34细胞及VSELs中的功能，以及其与CXCR4/SDF-1途径的关系，将推动再生医学中成人多能细胞应用领域的进展及其在白血病中作用的研究。
