The anti-fibrotic effects of mesenchymal stem cells on irradiated lungs via stimulating endogenous secretion of HGF and PGE2

Dong, Lihua; Jiang, Yiyao; Liu, Yongjun; Cui, Shuang; Xia, Chengcheng; Qu, Chao; Jiang, Xin; Qu, Yuanyuan; Chang, Pengyu; Liu, Feng

doi:10.1038/srep08713

Cited by 83 publications

(79 citation statements)

References 47 publications

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“…The beneficial effects of MSC-derived HGF observed in vitro (in terms of wound healing and apoptosis) were recapitulated in vivo with significant increases in HGF detected in lungs of mice receiving early administration of MSCs. Moreover, other studies have demonstrated elevated levels of HGF and decreased apoptosis in the lung following MSC administration, [37,55] supporting these findings.…”

Section: Discussionsupporting

confidence: 78%

Hepatocyte Growth Factor Is Required for Mesenchymal Stromal Cell Protection Against Bleomycin-Induced Pulmonary Fibrosis

Cahill

Kennelly

Carty

et al. 2016

Stem Cells Translational Medicine

102

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The incidence of idiopathic pulmonary fibrosis is on the rise and existing treatments have failed to halt or reverse disease progression. Mesenchymal stromal cells (MSCs) have potent cytoprotective effects, can promote tissue repair, and have demonstrated efficacy in a range of fibrotic lung diseases; however, the exact mechanisms of action remain to be elucidated. Chemical antagonists and short hairpin RNA knockdown were used to identify the mechanisms of action used by MSCs in promoting wound healing, proliferation, and inhibiting apoptosis. Using the bleomycin induced fibrosis model, the protective effects of early or late MSC administration were examined. The role for hepatocyte growth factor (HGF) in MSC protection against bleomycin lung injury was examined using HGF knockdown MSC. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling assay was performed on ex vivo lung sections to examine the effects of MSC on apoptosis. MSC conditioned media (CM) enhanced wound closure and inhibited apoptosis of pulmonary cells in vitro. HGF was required for MSC CM enhancement of epithelial cell proliferation and inhibition of apoptosis. In contrast, MSC required COX-2 for CM to inhibit fibroblast proliferation. In a murine model, early administration of MSC protected against bleomycin induced lung fibrosis and correlated with reduced levels of the proinflammatory cytokine interleukin-1b, reduced levels of apoptosis, and significantly increased levels of HGF. These protective effects were in part mediated by MSC derived HGF as HGF knockdown MSC were unable to protect against fibrosis in vivo. These findings delineate the mechanisms of MSC protection in a preclinical model of fibrotic lung disease. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1307-1318 SIGNIFICANCEThe mechanisms used by mesenchymal stromal cells (MSCs) in mediating protective effects in chronic models of lung disease are not understood and remain to be elucidated. These findings from in vitro studies highlight an important role for the MSC-derived soluble factors hepatocyte growth factor (HGF) and prostaglandin E 2 in promoting wound healing and inhibiting apoptosis. Furthermore, this study translates these findings demonstrating an important role for HGF in the protective effects mediated by MSC in vivo in the bleomycin model. These findings support a targeted approach to enhancing MSC therapy for fibrotic disease and highlight the importance of timing of MSC therapy.

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Section: Discussionsupporting

confidence: 78%

Hepatocyte Growth Factor Is Required for Mesenchymal Stromal Cell Protection Against Bleomycin-Induced Pulmonary Fibrosis

Cahill

Kennelly

Carty

et al. 2016

Stem Cells Translational Medicine

102

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“…151 Adipose-derived MSCs have also been used for ameliorating radiation-induced pulmonary fibrosis in Sprague-Dawley rats, whereby hepatocyte growth factor ( HGF ) and PGE2 levels increased and TNF-α and TGF-β1 levels decreased after MSC infusion. 152 Another example is the use of BM-MSCs to treat chronic obstructive pulmonary disease, where the BM-MSCs alleviate airway inflammation and emphysema by promoting the down-regulation of cyclooxygenase-2 (COX-2 ) and COX-2-mediated PGE2 production in alveolar macrophages through p38 and ERK. 153 …”

Section: Future Directions Of Mesenchymal Stem Cell Researchmentioning

confidence: 99%

Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

et al. 2016

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Mesenchymal stem cells (MSCs) are a group of fibroblast-like multipotent mesenchymal stromal cells that have the ability to differentiate into osteoblasts, adipocytes, and chondrocytes. Recent studies have demonstrated that MSCs possess a unique ability to exert suppressive and regulatory effects on both adaptive and innate immunity in an autologous and allogeneic manner. A vital step in stem cell transplantation is overcoming the potential graft-versus-host disease, which is a limiting factor to transplantation success. Given that MSCs attain powerful differentiation capabilities and also present immunosuppressive properties, which enable them to survive host immune rejection, MSCs are of great interest. Due to their ability to differentiate into different cell types and to suppress and modulate the immune system, MSCs are being developed for treating a plethora of diseases, including immune disorders. Moreover, in recent years, MSCs have been genetically engineered to treat and sometimes even cure some diseases, and the use of MSCs for cell therapy presents new perspectives for overcoming tissue rejection. In this review, we discuss the potential extrinsic and intrinsic mechanisms that underlie MSCs’ unique ability to modulate inflammation, and both innate and adaptive immunity.

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“…In a study of radiation-induced pulmonary fibrosis in Sprague Dawley rats, Dong et al showed a decrease in pro-fibrotic transforming growth factor-β and tumor necrosis factor-α after systemic MSC instillation (Dong et al 2015). The authors speculate that MSCs also inhibit lung fibrosis through the secretion of hepatocyte growth factor and prostaglandin.…”

Section: Mscs Stimulate Tissue Repairmentioning

confidence: 99%

Therapeutic potential of mesenchymal stem cells for diabetes

Moreira

Kahlenberg

Hornsby

2017

Journal of Molecular Endocrinology

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Mesenchymal stem cells (MSCs) are self-renewing multipotent cells that have the capacity to secrete multiple biologic factors that can restore and repair injured tissues. Preclinical and clinical evidence have substantiated the therapeutic benefit of MSCs in various medical conditions. Currently, MSCs are the most commonly used cell-based therapy in clinical trials because of their regenerative effects, ease of isolation, and low immunogenicity. Experimental and clinical studies have provided promising results using MSCs to treat diabetes. This review will summarize the role of MSCs on tissue repair, provide emerging strategies to improve MSC function, and describe how these processes translate to clinical treatments for diabetes.

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The anti-fibrotic effects of mesenchymal stem cells on irradiated lungs via stimulating endogenous secretion of HGF and PGE2

Cited by 83 publications

References 47 publications

Hepatocyte Growth Factor Is Required for Mesenchymal Stromal Cell Protection Against Bleomycin-Induced Pulmonary Fibrosis

Hepatocyte Growth Factor Is Required for Mesenchymal Stromal Cell Protection Against Bleomycin-Induced Pulmonary Fibrosis

Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

Therapeutic potential of mesenchymal stem cells for diabetes

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