Identifying the Efficacy of Extracellular Vesicles in Osteogenic Differentiation: An EV-Lution in Regenerative Medicine
Identifying the Efficacy of Extracellular Vesicles in Osteogenic Differentiation: An EV-Lution in Regenerative Medicine
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DOI：
10.3389/fdmed.2022.849724
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发表时间：
2022-03
期刊：
影响因子：
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通讯作者：
Sarah Brown;S. Dewitt;A. Clayton;R. Waddington
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文献类型：
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作者：
Sarah Brown;S. Dewitt;A. Clayton;R. Waddington
间充质间质细胞（MSCs）长期以来一直是再生医学和修复全身受损或衰老细胞的焦点。然而，MSCs在基于细胞的治疗中的疗效仍然是不可预测的，并且伴随着无数的风险。据估计，只有3-10%的间充质干细胞在移植后存活，并且在这些给药细胞群中仍然存在未定义和高度可变的异质生物效力。其作用模式指向由间充质干细胞产生的分泌因子，而不是依赖于移植。因此，利用这些分泌元素来替代活细胞疗法是很有吸引力的。细胞外囊泡（EVs）是由细胞分泌的异质脂质结合结构。它们由一系列复杂的分子组成，包括RNA、蛋白质和其他促进细胞间通讯的因素。作为受保护的信号中心，ev可以改变受体细胞的细胞活性，并且正在成为基于细胞的治疗的可靠替代方案。除了促进组织基质合成所需的细胞增殖和分化外，EV疗法还通过防止细胞凋亡、调节免疫反应和刺激血管生成，在伤口愈合中发挥有益作用。值得注意的是，EVs在移植后保持其信号功能，避免了与细胞治疗相关的问题。然而，就其作为药物的效用而言，电动汽车的研究仍处于起步阶段，围绕再生医学的电动汽车的机制理解，最佳来源和分离仍存在许多问题。这篇综述将考虑使用细胞来源的ev与传统的基于细胞的骨修复和再生疗法的疗效。我们讨论了在开发生产性调查线和建立标准化协议时需要考虑的因素，以便利用ev从最佳分泌组产生，提供可重复和有效的治疗。
Mesenchymal stromal cells (MSCs) have long been the focus for regenerative medicine and the restoration of damaged or aging cells throughout the body. However, the efficacy of MSCs in cell-based therapy still remains unpredictable and carries with it enumerable risks. It is estimated that only 3-10% of MSCs survive transplantation, and there remains undefined and highly variable heterogeneous biological potency within these administered cell populations. The mode of action points to secreted factors produced by MSCs rather than the reliance on engraftment. Hence harnessing such secreted elements as a replacement for live-cell therapies is attractive. Extracellular vesicles (EVs) are heterogenous lipid bounded structures, secreted by cells. They comprise a complex repertoire of molecules including RNA, proteins and other factors that facilitate cell-to-cell communication. Described as protected signaling centers, EVs can modify the cellular activity of recipient cells and are emerging as a credible alternative to cell-based therapies. EV therapeutics demonstrate beneficial roles for wound healing by preventing apoptosis, moderating immune responses, and stimulating angiogenesis, in addition to promoting cell proliferation and differentiation required for tissue matrix synthesis. Significantly, EVs maintain their signaling function following transplantation, circumventing the issues related to cell-based therapies. However, EV research is still in its infancy in terms of their utility as medicinal agents, with many questions still surrounding mechanistic understanding, optimal sourcing, and isolation of EVs for regenerative medicine. This review will consider the efficacy of using cell-derived EVs compared to traditional cell-based therapies for bone repair and regeneration. We discuss the factors to consider in developing productive lines of inquiry and establishment of standardized protocols so that EVs can be harnessed from optimal secretome production, to deliver reproducible and effective therapies.