1 Developmental BioEngineering, MIRA Institute for Biomedical Technology & Technical Medicine, University of Twente , Enschede, Netherlands.
2 Center for Craniofacial Molecular Biology, University of Southern California , Los Angeles, Los Angeles, California.
Tissue Eng Part B Rev. 2017 Dec;23(6):515-528. doi: 10.1089/ten.TEB.2016.0365.
Mesenchymal stem cells (MSCs) are considered to hold great therapeutic value for cell-based therapy and for tissue regeneration in particular. Recent evidence indicates that the main underlying mechanism for MSCs' beneficial effects in tissue regeneration is based on their capability to produce a large variety of bioactive trophic factors that stimulate neighboring parenchymal cells to start repairing damaged tissues. These new findings could potentially replace the classical paradigm of MSC differentiation and cell replacement. These bioactive factors have diverse actions like modulating the local immune system, enhancing angiogenesis, preventing cell apoptosis, and stimulating survival, proliferation, and differentiation of resident tissue specific cells. Therefore, MSCs are referred to as conductors of tissue repair and regeneration by secreting trophic mediators. In this review article, we have summarized the studies that focused on the trophic effects of MSC within the context of tissue regeneration. We will also highlight the various underlying mechanisms used by MSCs to act as trophic mediators. Besides the secretion of growth factors, we discuss two additional mechanisms that are likely to mediate MSC's beneficial effects in tissue regeneration, namely the production of extracellular vesicles and the formation of membrane nanotubes, which can both connect different cells and transfer a variety of trophic factors varying from proteins to mRNAs and miRNAs. Furthermore, we postulate that apoptosis of the MSCs is an integral part of the trophic effect during tissue repair.
间充质干细胞（MSCs）被认为在细胞治疗和组织再生方面具有巨大的治疗价值。最近的证据表明，MSCs 在组织再生中发挥有益作用的主要潜在机制是基于它们产生大量生物活性营养因子的能力，这些因子刺激邻近实质细胞开始修复受损组织。这些新发现可能会取代 MSC 分化和细胞替代的经典范例。这些生物活性因子具有多种作用，如调节局部免疫系统、促进血管生成、防止细胞凋亡以及刺激驻留组织特异性细胞的存活、增殖和分化。因此，MSCs 通过分泌营养介质被称为组织修复和再生的导体。在这篇综述文章中，我们总结了聚焦于 MSC 在组织再生背景下的营养作用的研究。我们还将强调 MSCs 作为营养介质发挥作用所使用的各种潜在机制。除了分泌生长因子外，我们还讨论了另外两种可能介导 MSC 在组织再生中有益作用的机制，即细胞外囊泡的产生和膜纳米管的形成，这两种机制都可以连接不同的细胞并传递各种营养因子，从蛋白质到 mRNAs 和 miRNAs 不等。此外，我们假设 MSC 的凋亡是组织修复过程中营养作用的一个组成部分。
