Amniotic MSCs reduce pulmonary fibrosis by hampering lung B-cell recruitment, retention, and maturation

Abstract

Growing evidence suggests a mechanistic link between inflammation and the development and progression of fibrotic processes. Mesenchymal stromal cells derived from the human amniotic membrane (hAMSCs), which display marked immunomodulatory properties, have been shown to reduce bleomycin‐induced lung fibrosis in mice, possibly by creating a microenvironment able to limit the evolution of chronic inflammation to fibrosis. However, the ability of hAMSCs to modulate immune cells involved in bleomycin‐induced pulmonary inflammation has yet to be elucidated. Herein, we conducted a longitudinal study of the effects of hAMSCs on alveolar and lung immune cell populations upon bleomycin challenge. Immune cells collected through bronchoalveolar lavage were examined by flow cytometry, and lung tissues were used to study gene expression of markers associated with different immune cell types. We observed that hAMSCs increased lung expression of T regulatory cell marker Foxp3, increased macrophage polarization toward an anti‐inflammatory phenotype (M2), and reduced the antigen‐presentation potential of macrophages and dendritic cells. For the first time, we demonstrate that hAMSCs markedly reduce pulmonary B‐cell recruitment, retention, and maturation, and counteract the formation and expansion of intrapulmonary lymphoid aggregates. Thus, hAMSCs may hamper the self‐maintaining inflammatory condition promoted by B cells that continuously act as antigen presenting cells for proximal T lymphocytes in injured lungs. By modulating B‐cell response, hAMSCs may contribute to blunting of the chronicization of lung inflammatory processes with a consequent reduction of the progression of the fibrotic lesion.

Amniotic membrane-mesenchymal stromal cells secreted factors and extracellular vesicle-miRNAs: Anti-inflammatory and regenerative features for musculoskeletal tissues

“…Similar findings were obtained also by Li et al on natural killer cells 6. The efficacy of hAMSC and their secreted factors was also confirmed in vivo in several animal models of diseases where the inflammatory component plays a prevalent role such as lung[102][103][104][105][106] and liver 107 fibrosis, wound healing,8,108,109 multiple sclerosis,110 inflammatory bowel disease,110 colitis,110,111 sepsis,110…”

Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells

“…Growing evidence suggests a mechanistic link between inflammation and pulmonary fibrosis as well as lung injury [ 138 , 139 ]. Studies showed that hAESCs were be able to attenuate the fetal pulmonary inflammatory response to experimental intrauterine inflammation and reduce consequent alterations in lung development [ 139 ] and furthermore, hAMSCs were showed to slow down the process of pulmonary fibrosis by reducing B-cell response which was induced in the chronicity of lung inflammatory processes [ 138 ]. Geng et al found that early hAESCs intervention was an effective way to delay disease progression in rats with chronic obstructive pulmonary disease (COPD) [ 140 ].…”

Perinatal Cells: A Promising COVID-19 Therapy?

“…The immunomodulatory activity of PDCs includes inhibition of immune cell (e.g., T and B lymphocyte) proliferation (Magatti et al, 2008 , 2020 ; Weiss et al, 2008 ; Najar et al, 2010a ; Prasanna et al, 2010 ; Raicevic et al, 2011 ; Zhou et al, 2011 ; Roy et al, 2013 ; Li et al, 2014 ; Wang et al, 2014 ; Pianta et al, 2016 ; Cargnoni et al, 2020 ; Papait et al, 2020 ), inhibition of the maturation toward effector immune cells (cells which actively respond to an immunogenic stimuli) (Magatti et al, 2009 ; Pianta et al, 2016 ), expansion of regulatory immune cells that can suppress the immune response (Chang et al, 2006 ; Najar et al, 2010b ; Parolini et al, 2014 ; Amari et al, 2015 ; Pianta et al, 2015 , 2016 ; Papait et al, 2020 ), inhibition of the secretion of pro-inflammatory cytokines and chemokines (IL-1β, IL-2, TNF -α, and IFN-γ) (Kronsteiner et al, 2011 ; Kang et al, 2012 ; Karlsson et al, 2012 ; Parolini et al, 2014 ; Pianta et al, 2015 ), involved in the aggravation of the inflammatory response, and promotion of the production of anti-inflammatory factors (IL-10, TGF-β), (Pianta et al, 2015 ; Papait et al, 2020 ).…”

“…Another recent study reported that administration of human placental MSC of fetal origin (hfPMSC), isolated from an unspecified region of placenta, in mice with bleomycin-induced lung fibrosis reduced collagen deposition and the production of pro-fibrotic cytokines by attenuating the dysregulation of MyD88/TGF-β signaling axis that is considered involved in the pathogenesis of pulmonary fibrosis in mice (Li et al, 2017 ). Finally, a very recent study demonstrates that hAMSC delivery in bleomycin-challenged mice reduces pulmonary B cell recruitment, retention and maturation, and counteract the formation and expansion of intrapulmonary lymphoid aggregates, thus dampening chronicization of lung inflammatory processes with a consequent reduction in fibrosis progression (Cargnoni et al, 2020 ).…”