Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies

Abstract

Background Pulmonary fibrosis (PF) is a devastating disease characterized by remodeling of lung architecture and abnormal deposition of fibroblasts in parenchymal tissue and ultimately results in respiratory failure and death. Preclinical studies suggest that mesenchymal stem cell (MSC) administration may be a safe and promising option in treating PF. The objective of our meta-analysis is to assess the efficacy of MSC therapy in preclinical models of PF. Methods We performed a comprehensive literature search in PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to March 17, 2021. Studies that assessed the efficacy of MSC therapy to animals with PF were included. The SYRCLE bias risk tool was employed to evaluate the bias of included studies. The primary outcomes included survival rate and pulmonary fibrosis scores. Meta-analysis was conducted via Cochrane Collaboration Review Manager (version 5.4) and Stata 14.0 statistical software. Results A total of 1120 articles were reviewed, of which 24 articles met inclusion criteria. Of these, 12 studies evaluated the survival rate and 20 studies evaluated pulmonary fibrosis scores. Compared to the control group, MSC therapy was associated with an improvement in survival rate (odds ratios (OR) 3.10, 95% confidence interval (CI) 2.06 to 4.67, P < 0.001, I2 = 0%) and a significant reduction in pulmonary fibrosis scores (weighted mean difference (WMD) 2.05, 95% CI −2.58 to −1.51, P < 0.001, I2 = 90%). Conclusions MSC therapy is a safe and effective method that can significantly improve the survival and pulmonary fibrosis of PF animals. These results provide an important basis for future translational clinical studies.

Mesenchymal stem cells in fibrotic diseases—the two sides of the same coin

“…Unlike the residential MSCs, implantations of external MSCs are reported with effective and protective functions in the treatment of fibrotic diseases in both pre-clinical and clinical studies [ 36 , 190 , 201 , 202 ]. These MSCs are in vitro amplified either from autologous (cells derived from the same individual) or allogeneic (cells derived from the same species but not the same individual) sources (Fig.…”

“…Surprisingly, greater therapeutic potential of MSCs was discovered as more complex functional mechanisms of these cells were revealed over the decades, including its immunomodulatory capabilities [ 18 ], autocrine and paracrine effects [ 19 ], and the abilities to escape from the innate immune system and counteract the complement system [ 20 ]. Therefore, the clinical application of MSCs has been extensively attempted for various diseases, such as osteoarthritis [ 21 ], rheumatoid arthritis [ 22 ], tissue repair [ 23 – 25 ], diabetic foot ulcer [ 26 ], diabetes [ 27 ], female infertility [ 28 ], autoimmune diseases [ 29 ], cardiovascular diseases [ 30 ], neurodegenerative diseases [ 31 ], graft versus host disease (GvHD) [ 32 ], COVID-19 patients [ 33 ], and different types of fibrotic diseases [ 34 – 36 ].…”

Umbilical cord-derived mesenchymal stem cell transplantation for COVID -19 patients: long-term benefits for lung regeneration

“…In other studies, MSCs showed anti-fibrotic effects on irradiated lungs via endogenous secretion of HGF and PGF2 19 and robust regulatory T-cell induction in bleomycin-induced pulmonary fibrosis 20 . In a metaanalysis of preclinical studies, Li et al (2021) analyzed 24 articles on the treatment of pulmonary fibrosis in an animal model using MSCs; this analysis showed that MSC therapy improved the survival rate and reduced pulmonary fibrosis scores 21 . In a recent review, Chen et al…”

Single-Cell RNA Sequencing Reveals the Interaction of Injected ADSCs with Lung-Originated Cells in Mouse Pulmonary Fibrosis

“…PF is traditionally considered to be an irreversible lung disease that is refractory to various treatments, resulting in high rates of mortality and morbidity [ 9 ]. Recently, the administration of mesenchymal stem cells (MSCs) has emerged as a promising therapy for PF [ 10 , 11 ]. MSCs have been isolated from various tissues such as the bone marrow, adipose tissue, and the stroma of organs.…”