Symbiosis Centre for Stem Cell Research, Symbiosis International (Deemed University), Pune, 412115, India.
Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Pune, 412115, India.
Cell Biol Int. 2020 May;44(5):1078-1102. doi: 10.1002/cbin.11313. Epub 2020 Feb 13.
Hematopoietic stem cell transplantation (HSCT) is the ultimate choice of treatment for patients with hematological diseases and cancer. The success of HSCT is critically dependent on the number and engraftment efficiency of the transplanted donor hematopoietic stem cells (HSCs). Various studies show that bone marrow-derived mesenchymal stromal cells (MSCs) support hematopoiesis and also promote ex vivo expansion of HSCs. MSCs exert their therapeutic effect through paracrine activity, partially mediated through extracellular vesicles (EVs). Although the physiological function of EVs is not fully understood, inspiring findings indicate that MSC-derived EVs can reiterate the hematopoiesis, supporting the ability of MSCs by transferring their cargo containing proteins, lipids, and nucleic acids to the HSCs. The activation state of the MSCs or the signaling mechanism that prevails in them also defines the composition of their EVs, thereby influencing the fate of HSCs. Modulating or preconditioning MSCs to achieve a specific composition of the EV cargo for the ex vivo expansion of HSCs is, therefore, a promising strategy that can overcome several challenges associated with the use of naïve/unprimed MSCs. This review aims to speculate upon the potential role of preconditioned/primed MSC-derived EVs as "cell-free biologics," as a novel strategy for expanding HSCs in vitro.
造血干细胞移植（HSCT）是治疗血液系统疾病和癌症患者的最终选择。HSCT 的成功与否关键取决于移植供体造血干细胞（HSCs）的数量和植入效率。各种研究表明，骨髓来源的间充质基质细胞（MSCs）支持造血，也促进 HSCs 的体外扩增。MSCs 通过旁分泌活性发挥其治疗作用，部分通过细胞外囊泡（EVs）介导。尽管 EVs 的生理功能尚未完全阐明，但令人鼓舞的发现表明，MSC 衍生的 EVs 可以重复造血，通过将其包含蛋白质、脂质和核酸的货物转移到 HSCs 中来支持 MSCs 的能力。MSCs 的激活状态或占主导地位的信号机制也定义了它们 EV 的组成，从而影响 HSCs 的命运。因此，调节或预处理 MSCs 以实现 HSCs 体外扩增的 EV 货物的特定组成是一种很有前途的策略，可以克服与使用原始/未成熟 MSCs 相关的几个挑战。本综述旨在推测预处理/预刺激 MSC 衍生 EV 作为“无细胞生物制剂”的潜在作用，作为体外扩增 HSCs 的一种新策略。
