Paracrine factors from mesenchymal stem cells attenuate epithelial injury and lung fibrosis

Shen, Qing; Chen, Bing; Xiao, Zhifeng; Zhao, Lifen; Xu, Xuefeng; Wan, Xin; Jin, Mulan; Dai, Jianwu; Dai, Huaping

doi:10.3892/mmr.2014.3092

Cited by 71 publications

(55 citation statements)

References 40 publications

(49 reference statements)

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“…MSCs have the ability to specifically target sites of injury, leading to antiapoptotic properties, modulation of immune responses, repair of epithelial tissues, attenuation of extracellular matrix deposition, and modification of the microenvironment at the engraftment sites [, ]. In addition to direct cell‐cell interaction, MSCs also act via a paracrine mechanism in secreting soluble factors that account for anti‐inflammatory and antifibrotic effects in vitro and in vivo [, ]. However, a major challenge that is limiting the potential of MSC‐based cell therapy is the extensive loss of transplanted cells and low paracrine activities due to exposure to harsh microenvironmental conditions and inflammation [].…”

Section: Introductionmentioning

confidence: 99%

Oncostatin M-Preconditioned Mesenchymal Stem Cells Alleviate Bleomycin-Induced Pulmonary Fibrosis Through Paracrine Effects of the Hepatocyte Growth Factor

Lan

Theng

Huang

et al. 2016

Stem Cells Translational Medicine

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Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti‐inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM‐preconditioned MSCs. OSM‐preconditioned MSCs were shown to overexpress type 2 OSM receptor (gp130/OSMRβ) and exhibited high susceptibility to OSM, resulting in upregulation of the paracrine factor, hepatocyte growth factor (HGF). Moreover, OSM‐preconditioned MSCs enhanced cell proliferation and migration, attenuated transforming growth factor‐β1‐ or OSM‐induced extracellular matrix production in MRC‐5 fibroblasts through paracrine effects. In bleomycin‐induced lung fibrotic mice, transplantation of OSM‐preconditioned MSCs significantly improved pulmonary respiratory functions and downregulated expression of inflammatory factors and fibrotic factors in the lung tissues. Histopathologic examination indicated remarkable amelioration of the lung fibrosis. LacZ‐tagged MSCs were detected in the lung tissues of the OSM‐preconditioned MSC‐treated mice 18 days after post‐transplantation. Taken together, our data further demonstrated that HGF upregulation played an important role in mediating the therapeutic effects of transplanted OSM‐preconditioned MSCs in alleviating lung fibrosis in the mice. Stem Cells Translational Medicine 2017;6:1006–1017

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Section: Introductionmentioning

confidence: 99%

Oncostatin M-Preconditioned Mesenchymal Stem Cells Alleviate Bleomycin-Induced Pulmonary Fibrosis Through Paracrine Effects of the Hepatocyte Growth Factor

Lan

Theng

Huang

et al. 2016

Stem Cells Translational Medicine

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“…Moreover, MSCs were also shown to regulate epithelial cells, DCs, etc. [39, 40], which is a research emphasis for the future.…”

Section: Discussionmentioning

confidence: 99%

The lncRNAs involved in mouse airway allergic inflammation following induced pluripotent stem cell-mesenchymal stem cell treatment

Wang

Fan

et al. 2017

Stem Cell Res Ther

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BackgroundWe have previously reported that induced pluripotent stem cell (iPSC)-mesenchymal stem cells (MSCs) alleviated asthma inflammation in mice. Long noncoding RNAs (lncRNAs) were recently reported as being involved in the immune responses. However, whether lncRNAs are associated with iPSC-MSC immunomodulation in allergic inflammation is still unclear.MethodsMice were induced into an asthmatic state and received treatment consisting of iPSC-MSCs. Memory T cells isolated from sensitized mice were challenged and co-cultured with iPSC-MSCs in vitro. Total RNA from the lungs and separated T cells were processed with an lncRNA/mRNA microarray. A series of bioinformatics technologies were used to screen the target lncRNAs.ResultsiPSC-MSCs significantly prevented asthma inflammation and decreased the Th2 cytokine levels. Over 1300 lncRNAs were differentially expressed after the induction of asthma, and 846 or 4176 lncRNAs were differentially expressed with iPSC-MSC treatment in mice or in vitro, respectively. After overlapping the differentially expressed lncRNAs produced in a similar manner in mice and in vitro, 23 lncRNAs and 96 mRNAs were selected, in which 58 protein-coding genes were predicted to be potential targets of the 23 lncRNAs. Furthermore, using a series of bioinformatics technologies, 9 lncRNAs co-expressed with the most differentially expressed mRNAs, which were enriched in terms of the immune response, were screened out via Pearson’s correlation coefficient with mRNAs that were involved with inflammatory cytokines and receptors. lncRNAs MM9LINCRNAEXON12105+ and AK089315 were finally emphasized via quantitative real-time PCR validation.ConclusionsOur results suggested that aberrant lncRNA profiles were present after asthma induction and iPSC-MSC treatment, suggesting potential targets of allergic inflammation and iPSC-MSC-mediated immunomodulation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0456-3) contains supplementary material, which is available to authorized users.

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“…Additionally, they also regulate T-cell activity [20,21]. Along with MSC administration, the extracellular vesicles or microvesicles secreted by the cells and conditioned medium may also be used for disease treatment [22,23]. In the present study, we examined the effect of administration of pre-conditioned MSC in a mouse model of idiopathic pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Effect of CoCl2 or H2O2 pre-conditioned mesenchymal stem cells in a mouse model of pulmonary fibrosis

2018

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Introduction: Pulmonary Fibrosis is characterized by excessive matrix deposition which leads to airway remodeling and disruption of the typical architecture of the lung parenchyma. The disease progression is associated with a high mortality rate. The current treatment for pulmonary fibrosis includes drugs which either reduce progression of the disease or provide symptomatic relief. Multiple studies have examined the effect of cell-based therapy in pulmonary fibrosis. We investigated the effect of administration of pre-conditioned bone marrow-derived mesenchymal stem cells (BMMSC) in a mouse model of pulmonary fibrosis. Methods: Firstly, we examined the effect of pre-conditioning on the cells using cell-based assays. We found that pre-conditioning did not significantly alter cell proliferation or led to cellular inflammation. The cells continued to express MSC marker, CD105, and pluripotency marker Oct3/4. Next, we evaluated the proliferative and anti-inflammatory potential of BMMSC administration using a series of assays in a mouse model of pulmonary fibrosis. Bleomycin was administered to induce pulmonary fibrosis in mice on Day 0. MSCs were administered on day 1 and day 3; the mice were sacrificed on day 22, and their tissues were collected for analysis. Results: We found that similar to untreated cells, administration of pre-conditioned cells resulted in an increase in the proliferative potential and reduction in inflammation in the lung tissue, bronchoalveolar lavage, bone marrow, and blood. We observed reduction in the number of granulocytes in peripheral blood upon MSC administration. However, we did not observe any structural changes in the lung upon MSC administration. We found a small reduction in collagen content in the lung which was also seen upon staining with Masson's trichrome. Conclusion: These results demonstrate that pre-conditioned BM-MSC lead to improvement in the disease state through paracrine effects but pre-conditioning of cells for 24 hours does not significantly improve the beneficial effect of MSC administration.

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Paracrine factors from mesenchymal stem cells attenuate epithelial injury and lung fibrosis

Abstract: Abstract. Paracrine factors are currently considered to be the major mechanism through which mesenchymal stem cells (MSCs) exert their actions.

Cited by 71 publications

References 40 publications

Oncostatin M-Preconditioned Mesenchymal Stem Cells Alleviate Bleomycin-Induced Pulmonary Fibrosis Through Paracrine Effects of the Hepatocyte Growth Factor

Oncostatin M-Preconditioned Mesenchymal Stem Cells Alleviate Bleomycin-Induced Pulmonary Fibrosis Through Paracrine Effects of the Hepatocyte Growth Factor

The lncRNAs involved in mouse airway allergic inflammation following induced pluripotent stem cell-mesenchymal stem cell treatment

Effect of CoCl2 or H2O2 pre-conditioned mesenchymal stem cells in a mouse model of pulmonary fibrosis

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