Mesenchymal stem cells regulate the Th17/Treg cell balance partly through hepatocyte growth factor in vitro

Chen, Qihong; Wu, Fei; Liu, Lei; Chen, Han-bing; Zheng, Ruiqiang; Wang, Hua-Ling; Yu, Lina

doi:10.1186/s13287-020-01612-y

Cited by 61 publications

(61 citation statements)

References 32 publications

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“…The application of stem cells may also play a part in the protection of the transplanted beta-cells. Such an impact is due to the ability to induce the proliferation of Tregs and the promotion of neovascularization (Caballero et al, 2007;Chen et al, 2020). Thus, a hybrid transplantation, which combined islet transplantation with mesenchymal stem cells, was shown to improve graft function (Figliuzzi et al, 2009).…”

Section: Methods For Beta-cell Preservationmentioning

confidence: 99%

Advances and complications of regenerative medicine in diabetes therapy

Brovkina

Дашинимаев

2020

PeerJ

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The rapid development of technologies in regenerative medicine indicates clearly that their common application is not a matter of if, but of when. However, the regeneration of beta-cells for diabetes patients remains a complex challenge due to the plurality of related problems. Indeed, the generation of beta-cells masses expressing marker genes is only a first step, with maintaining permanent insulin secretion, their protection from the immune system and avoiding pathological modifications in the genome being the necessary next developments. The prospects of regenerative medicine in diabetes therapy were promoted by the emergence of promising results with embryonic stem cells (ESCs). Their pluripotency and proliferation in an undifferentiated state during culture have ensured the success of ESCs in regenerative medicine. The discovery of induced pluripotent stem cells (iPSCs) derived from the patients’ own mesenchymal cells has provided further hope for diabetes treatment. Nonetheless, the use of stem cells has significant limitations related to the pluripotent stage, such as the risk of development of teratomas. Thus, the direct conversion of mature cells into beta-cells could address this issue. Recent studies have shown the possibility of such transdifferentiation and have set trends for regeneration medicine, directed at minimizing genome modifications and invasive procedures. In this review, we will discuss the published results of beta-cell regeneration and the advantages and disadvantages illustrated by these experiments.

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Section: Methods For Beta-cell Preservationmentioning

confidence: 99%

Advances and complications of regenerative medicine in diabetes therapy

Brovkina

Дашинимаев

2020

PeerJ

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“…This effect seems to be partially dependent on IDO, as the impact was less prominent in IDO knock-out MSCs. Novel findings indicated that the inhibition of Th17 cells by murine MSCs is also mediated by HGF ( Chen et al, 2020 ). Furthermore, it has been reported that BM-MSCs impair the IL-17 production by Th17 cells in a contact-dependent manner and induce their interconversion into Tregs ( Luz-Crawford et al, 2019 ).…”

Section: Regulation Of Adaptive Immunity By Mscsmentioning

confidence: 99%

Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update

Müller

Tunger

Wobus

et al. 2021

Front. Cell Dev. Biol.

110

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Mesenchymal stromal cells (MSCs) are characterized by an extraordinary capacity to modulate the phenotype and functional properties of various immune cells that play an essential role in the pathogenesis of inflammatory disorders. Thus, MSCs efficiently impair the phagocytic and antigen-presenting capacity of monocytes/macrophages and promote the expression of immunosuppressive molecules such as interleukin (IL)-10 and programmed cell death 1 ligand 1 by these cells. They also effectively inhibit the maturation of dendritic cells and their ability to produce proinflammatory cytokines and to stimulate potent T-cell responses. Furthermore, MSCs inhibit the generation and proinflammatory properties of CD4+ T helper (Th)1 and Th17 cells, while they promote the proliferation of regulatory T cells and their inhibitory capabilities. MSCs also impair the expansion, cytokine secretion, and cytotoxic activity of proinflammatory CD8+ T cells. Moreover, MSCs inhibit the differentiation, proliferation, and antibody secretion of B cells, and foster the generation of IL-10-producing regulatory B cells. Various cell membrane-associated and soluble molecules essentially contribute to these MSC-mediated effects on important cellular components of innate and adaptive immunity. Due to their immunosuppressive properties, MSCs have emerged as promising tools for the treatment of inflammatory disorders such as acute graft-versus-host disease, graft rejection in patients undergoing organ/cell transplantation, and autoimmune diseases.

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“…Some studies showed that the production of hepatocyte growth factor (HGF) by MSCs can partially modulate the Treg/Th17 balance. An in vitro study using MSC co-cultured in transwell with CD4 + T cells activated with LPS proposed that HGF is necessary for an increased number of CD4 + Foxp3 + cells and a downregulated number of CD4 + RORγt + cells [ 135 ]. In an in vivo model of bronchiolitis obliterans in mice, the infusion of umbilical cord-derived MSCs overexpressing HGF improved the Th1/Th2 ratio, increased the number of Treg cells, and decreased the number of Th17 cells in the spleen; these results were accompanied by decreased IFN-γ levels and increased IL-4 and IL-10 levels in serum [ 136 ].…”

Section: Mechanisms Behind the Msc Immunosuppressive Effect On Th1mentioning

confidence: 99%

Mechanisms behind the Immunoregulatory Dialogue between Mesenchymal Stem Cells and Th17 Cells

Terraza-Aguirre

Campos‐Mora

Elizondo‐Vega

et al. 2020

Cells

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Mesenchymal stem cells (MSCs) exhibit potent immunoregulatory abilities by interacting with cells of the adaptive and innate immune system. In vitro, MSCs inhibit the differentiation of T cells into T helper 17 (Th17) cells and repress their proliferation. In vivo, the administration of MSCs to treat various experimental inflammatory and autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and bowel disease showed promising therapeutic results. These therapeutic properties mediated by MSCs are associated with an attenuated immune response characterized by a reduced frequency of Th17 cells and the generation of regulatory T cells. In this manuscript, we review how MSC and Th17 cells interact, communicate, and exchange information through different ways such as cell-to-cell contact, secretion of soluble factors, and organelle transfer. Moreover, we discuss the consequences of this dynamic dialogue between MSC and Th17 well described by their phenotypic and functional plasticity.

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Mesenchymal stem cells regulate the Th17/Treg cell balance partly through hepatocyte growth factor in vitro

Cited by 61 publications

References 32 publications

Advances and complications of regenerative medicine in diabetes therapy

Advances and complications of regenerative medicine in diabetes therapy

Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update

Mechanisms behind the Immunoregulatory Dialogue between Mesenchymal Stem Cells and Th17 Cells

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