Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
Department of Regenerative Medicine, Center for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland.
Leukemia. 2020 Dec;34(12):3126-3135. doi: 10.1038/s41375-020-01041-z. Epub 2020 Sep 14.
There are concepts in science that need time to overcome initial disbelief before finally arriving at the moment when they are embraced by the research community. One of these concepts is the biological meaning of the small, spheroidal vesicles released from cells, which are described in the literature as microparticles, microvesicles, or exosomes. In the beginning, this research was difficult, as it was hard to distinguish these small vesicles from cell debris or apoptotic bodies. However, they may represent the first language of cell-cell communication, which existed before a more specific intercellular cross-talk between ligands and receptors emerged during evolution. In this review article, we will use the term "extracellular microvesicles" (ExMVs) to refer to these small spheroidal blebs of different sizes surrounded by a lipid layer of membrane. We have accepted an invitation from the Editor-in-Chief to write this review in observance of the 20th anniversary of the 2001 ASH Meeting when our team demonstrated that, by horizontal transfer of several bioactive molecules, including mRNA species and proteins, ExMVs harvested from embryonic stem cells could modify hematopoietic stem/progenitor cells and expand them ex vivo. Interestingly, the result that moved ExMV research forward was published first in 2005 in Leukemia, having been previously rejected by other major scientific journals out of simple disbelief. Therefore, the best judge of a new concept is the passage of time, although the speed of its adoption is aided by perseverance and confidence in one's own data. In this perspective article, we will provide a brief update on the current status of, hopes for, and likely future of ExMV research as well as therapeutic and diagnostic applications, with a special emphasis on hematopoiesis.
科学界有些概念需要时间克服最初的怀疑，才能最终被研究界所接受。其中一个概念是细胞释放的小球形小泡的生物学意义，这些小泡在文献中被描述为微泡、微囊泡或外泌体。起初，这项研究很困难，因为很难将这些小泡与细胞碎片或凋亡小体区分开来。然而，它们可能代表了细胞间通讯的第一种语言，这种语言存在于进化过程中配体和受体之间更具体的细胞间通讯出现之前。在这篇综述文章中，我们将使用“细胞外微泡”（ExMVs）来指代这些大小不一的球形小泡，它们被一层脂质膜包围。我们接受了主编的邀请，撰写这篇综述，以纪念 2001 年 ASH 会议 20 周年，当时我们的团队证明，通过水平转移几种生物活性分子，包括 mRNA 种类和蛋白质，从胚胎干细胞中提取的 ExMVs 可以修饰造血干/祖细胞并在体外扩增它们。有趣的是，推动 ExMV 研究前进的结果首先于 2005 年在《白血病》上发表，此前被其他主要科学期刊因单纯的怀疑而拒绝。因此，新概念的最佳评判者是时间的流逝，尽管其采用速度得益于对自己数据的坚持和信心。在这篇观点文章中，我们将简要介绍 ExMV 研究的现状、希望和未来以及治疗和诊断应用，特别强调造血。
