Anti‐fibrotic effects of different sources of MSC in bleomycin‐induced lung fibrosis in C57BL6 male mice

Abstract

Background and objectiveIPF is a fatal and debilitating lung disorder increasing in incidence worldwide. To date, two approved treatments only slow disease progression, have multiple side effects and do not provide a cure. MSC have promising therapeutic potential as a cell‐based therapy for many lung disorders based on the anti‐fibrotic properties of the MSC.MethodsCritical questions remain surrounding the optimal source, timing and efficacy of cell‐based therapies. The present study examines the most effective sources of MSC. Human MSC were derived from adipose, WJ, chorionic membrane (CSC) and chorionic villi (CVC). MSC were injected into the ageing mouse model of BLM‐induced lung fibrosis.ResultsAll sources decreased Aschroft and hydroxyproline levels when injected into BLM‐treated mice at day 10 with the exception of CSC cells that did not change hydroxyproline levels. There were also decreases in mRNA expression of αv‐integrin and TNFα in all sources except CSC. Only ASC‐ and WJ‐derived cells reduced AKT and MMP‐2 activation, while Cav‐1 was increased by ASC treatment as previously reported. BLM‐induced miR dysregulation of miR‐29 and miR‐199 was restored only by ASC treatment.ConclusionOur data suggest that sources of MSC may differ in the pathway(s) involved in repair.

The ongoing quest for a fountain of youth: Cell therapy for pulmonary fibrosis

“…All MSC except those derived from whole chorion reduced fibrosis in the ageing mouse model; however, there were notable differences in the effect on mediators including microRNA. Contrary to the authors' original hypothesis, some of the most profound effects were seen in mice treated with MSC derived from adult adipose tissue 8 …”

“…Contrary to the authors' original hypothesis, some of the most profound effects were seen in mice treated with MSC derived from adult adipose tissue. 8 What can we infer from the work of Pereira-Simon et al? Fittingly, their laboratory, headed by Marilyn Glassberg, is located in Florida which in the 1500s was thought to be the location of the 'fountain of youth', prompting significant but ultimately unsuccessful Spanish exploration.…”

“…In a recent publication in Respirology, Pereira-Simon et al undertake an exhaustive set of experiments to understand whether, even amongst young cells, regenerative potential can vary. 8 Importantly, in the context of a contemporary understanding of PF-ILD pathogenesis, they studied the effect of various mesenchymal stem cell (MSC) sources in the ageing mouse model of bleomycin-induced lung fibrosis. Other than embryonic and induced pluripotent stem cells, MSC are the most studied in the context of human disease.…”

Therapeutic Applications of Mesenchymal Stem Cells in Idiopathic Pulmonary Fibrosis

“…Only AD-MSCs restored BLM-induced miR dysregulation of miR-29 and miR-199. These results showed that sources of MSCs might differ in their repair functions and underlying mechanisms (Periera-Simon et al, 2021). The latest single-cell RNA sequencing study has identified very significant transcriptional overlap between WJ-and AD-MSCs, thus potentially explaining some of these findings (Sun et al, 2020).…”

“…IL-10, interleukin-10; IL-4, interleukin-4; IL-1ra, IL-1 receptor antagonist; IFN-γ, interferon-γ; PGE2, prostaglandin E2; IDO-1, indolamine 2,3-dioxygenase-1; Ang-1, angiogenin-1; HGF, hepatocyte growth factor; KGF, keratinocyte growth factor. experimental protocols include the isolation of MSCs, plastic adherent cultures, harvesting of logarithmic growth phase cells, and adoptive transplantation in animal models of pulmonary fibrosis (Zhang et al, 2019;Gad et al, 2020;Periera-Simon et al, 2021). Although MSCs can reduce fibrosis, the various experimental variables obfuscate direct comparisons between different experiments.…”