Roles of Mesenchymal Stem Cells in Tissue Regeneration and Immunomodulation

Abstract

Mesenchymal stem cells are classified as multipotent stem cells, due to their capability to transdifferentiate into various lineages that develop from mesoderm. Their popular appeal as cell-based therapy was initially based on the idea of their ability to restore tissue because of their differentiation potential ; however, the lack of evidence of their differentiation to target cells led researchers to focus on their secreted trophic factors and their role as potential powerhouses on regulation of factors under different immunological environments and recover homeostasis. To date there are more than 800 clinical trials on humans related to MSCs as therapy, not to mention that in animals is actively being applied as therapeutic resource, though it has not been officially approved as one. But just as how results from clinical trials are important, so is to reveal the biological mechanisms involved on how these cells exert their healing properties to further enhance the application of MSCs on potential patients. In this review, we describe characteristics of MSCs, evaluate their benefits as tissue regenerative therapy and combination therapy, as well as their immunological properties, activation of MSCs that dictate their secreted factors, interactions with other immune cells, such as T cells and possible mechanisms and pathways involved in these interactions.

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

“…Engela et al demonstrated that Treg cells can induce IDO secretion in MSCs, which results in TNF-α reduction and induction of IL-10 in Treg cells and effector cells [286]. Different subtypes of Treg cells generated by MSCs have been identified including CD4 + CD25 + Foxp3 + Treg cells and IL-10 producing type 1 Treg (Tr1) cells [287]. There is a complex cross-talk between MSCs and macrophages, which cannot be simply explained by MSCderived anti-inflammatory factors.…”

Defining a Regulatory Strategy for ATMP/Aerosol Delivery Device Combinations in the Treatment of Respiratory Disease

“…One cell type, in particular, under intense investigation for its potential utility in the treatment of a variety of human diseases are mesenchymal stromal cells (MSCs). The interest in MSC therapy is largely due to their accessibility from adult tissue, their multilineage differentiation potential, and their diverse mechanism of action through both cryoprotective and paracrine effects, as well as their low immunogenicity [ 14 , 15 , 16 ].…”

Progress in research on functional mechanisms of mesenchymal stem cells

“…研究发现, MSC产生的生物活性物质参与 Figure 2 Bioactive substances produced by MSCs [27] 是通过一氧化氮合成酶(inducible nitric oxide synthase, iNOS)产生大量NO在抑制淋巴细胞活性方面发挥关 键作用 [28] . MSCs产生的多种免疫调节因子之间可通 过协同或拮抗发挥作用, 不仅参与免疫反应的调控, 而且还参与炎症反应的应答和组织损伤修复等多个生 物学进程 [29,30] .…”