Therapeutic potential of adipose stem cell‐derived conditioned medium against pulmonary hypertension and lung fibrosis

Rathinasabapathy, Anandharajan; Bruce, Eugene N.; Espejo, Andrew; Horowitz, Alana; Sudhan, Dhivya R.; Nair, Anand; Guzzo, Dominic; Francis, Joseph; Raizada, Mohan K.; Shenoy, Vinayak; Katovich, Michael J.

doi:10.1111/bph.13562

Cited by 46 publications

(52 citation statements)

References 68 publications

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“…To test the functional effects of exosomes, we employed a Bleo-induced PF model in SD rats similar to the mouse model previously presented ( Fig. 5d) 21 . By utilizing rats in this study we were able to measure pulmonary function and evaluate the respiratory system mechanics using the forced oscillation techniques employed by the FlexiVent.…”

Section: Lsc Secretome Therapy In Silica-induced Pulmonary Fibrosismentioning

confidence: 99%

Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

et al. 2020

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Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin-and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis.

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Section: Lsc Secretome Therapy In Silica-induced Pulmonary Fibrosismentioning

confidence: 99%

Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

et al. 2020

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“…Stem cell therapy may constitute a new treatment modality for PAH [ 14 , 15 ]. Particularly, mesenchymal stromal cells (MSCs) may have the ability to secrete paracrine factors which can mitigate tissue damage [ 16 ]. Preclinical studies using MSCs in animals with PAH reported reduction in inflammation [ 16 ] and remodeling [ 17 – 20 ], which may be associated with improvement in hemodynamics [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…Particularly, mesenchymal stromal cells (MSCs) may have the ability to secrete paracrine factors which can mitigate tissue damage [ 16 ]. Preclinical studies using MSCs in animals with PAH reported reduction in inflammation [ 16 ] and remodeling [ 17 – 20 ], which may be associated with improvement in hemodynamics [ 19 ]. However, those studies evaluated lung vascular remodeling based on either RV ratios [ 18 , 19 ] or basic wall thickness [ 17 , 20 ], instead of fulfilling histological criteria for PAH [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension

et al. 2017

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BackgroundExperimental research has reported beneficial effects of mesenchymal stromal cell (MSC) therapy in pulmonary arterial hypertension (PAH). However, these studies either were based on prophylactic protocols or assessed basic remodeling features without evaluating possible mechanisms. We analyzed the effects of MSC therapy on lung vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH.MethodsTwenty-eight Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, while a control group received saline (SAL) instead. On day 14, both groups were further randomized to receive 105 adipose-derived MSCs or SAL intravenously (n = 7/group). On day 28, right ventricular systolic pressure (RVSP) and the gene expression of mediators associated with apoptosis, inflammation, fibrosis, Smad-1 levels, cell proliferation, and endothelial–mesenchymal transition were determined. In addition, lung histology (smooth muscle cell proliferation and plexiform-like injuries), CD68+ and CD163+ macrophages, and plasma levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were evaluated.ResultsIn the PAH group, adipose-derived MSCs, compared to SAL, reduced mean RVSP (29 ± 1 vs 39 ± 2 mmHg, p < 0.001), lung tissue collagen fiber content, smooth muscle cell proliferation, CD68+ macrophages, interleukin-6 expression, and the antiapoptotic mediators Bcl-2 and survivin. Conversely, expression of the proapoptotic mediator procaspase-3 and plasma VEGF increased, with no changes in PDGF. In the pulmonary artery, MSCs dampened the endothelial–mesenchymal transition.ConclusionIn MCT-induced PAH, MSC therapy reduced lung vascular remodeling, thus improving hemodynamics. These beneficial effects were associated with increased levels of proapoptotic markers, mesenchymal-to-endothelial transition, reduced cell proliferation markers, and inflammation due to a shift away from the M1 phenotype.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0669-0) contains supplementary material, which is available to authorized users.

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“…In the present study, it was demonstrated that BMSCs may engraft into injured lung tissue and reduce the lung epithelium damage, which is beneficial for lung repair following PQ exposure. �lthough the precise mechanism of action of MSCs remains elusive (25), in a number of clinical trials (50,51) it was demonstrated that MSCs may have the ability to produce paracrine factors that may mitigate tissue damage (52). The paracrine factors released by MSCs may alter the microenvironment and contribute to a repairing effect in pulmonary fibrosis (50).…”

Section: Discussionmentioning

confidence: 99%

Role of bone marrow mesenchymal stem cells in the development of PQ‑induced pulmonary fibrosis

Chen

Zhou

et al. 2019

Mol Med Report

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Paraquat (PQ) poisoning-induced pulmonary fibrosis is one of the primary causes of mortality in patients with PQ poisoning. The potential mechanism of PQ-induced pulmonary fibrosis was thought to be mediated by inflammation. Recently, bone marrow-derived mesenchymal stem cells (BMSCs) have been considered as a potential strategy for the treatment of fibrotic disease due to their anti-inflammatory and immunosuppressive effects. In the present study, an increased accumulation of BMSCs in a mouse model of PQ-induced pulmonary fibrosis following their transplantation, markedly improving the survival rate of mice with PQ poisoning. In addition, the results indicated that BMSC transplantation may inhibit the production of pro-inflammatory cytokines, including tumor necrosis factor-α interleukin (IL)-1β, IL-6 and IL-10 in the lung tissues of PQ-poisoned mice, and ultimately attenuate the pulmonary fibrosis. In vitro, BMSCs may suppress PQ-induced epithelial-to-mesenchymal transition and protect pulmonary epithelial cells from PQ-induced apoptosis. These findings suggest that BMSC transplantation may be a promising treatment for pulmonary fibrosis induced by PQ poisoning.

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Therapeutic potential of adipose stem cell‐derived conditioned medium against pulmonary hypertension and lung fibrosis

Abstract: Our study indicates that CM treatment is as effective as ASCs in treating PH and PF. These beneficial effects of CM may provide an innovative approach to treat cardiopulmonary disorders.

Cited by 46 publications

References 68 publications

Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension

Role of bone marrow mesenchymal stem cells in the development of PQ‑induced pulmonary fibrosis

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