Mesenchymal Stromal Cells Derived Conditioned Medium in Pulmonary Fibrosis: A Systematic Review and Meta-analysis

Abstract

Background: A definitive conclusion on the efficacy of mesenchymal stromal cells-derived conditioned medium (MSCs-CM) in pulmonary fibrosis has not yet been reached. Therefore, the present meta-analysis intends to investigate the efficacy of MSCs-CM administration on improvement of pulmonary fibrosis. Methods: An extensive search was performed on the Medline, Embase, Scopus and Web of Science databases by the end of August 2019. Outcomes in the present study included pulmonary fibrosis score, lung collagen deposition, lung collagen expression, transforming growth factor β1 (TGF-β1) expression and interleukin-6 expression. Finally, the data were pooled and an overall standardized mean difference (SMD) with a 95% confidence interval (CI) was reported. Results: Data from seven studies were included. Analyses showed that administration of MSCs-CM significantly improved pulmonary fibrosis (SMD = -2.36; 95% CI: -3.21, -1.51). MSCs-CM administration also attenuated lung collagen deposition (SMD = -1.70; 95% CI: -2.18, -1.23) and decreased expression of type I collagen (SMD = -6.27; 95% CI: -11.00, -1.55), type III collagen (SMD = -5.16; 95% CI: -9.86, -0.47), TGF- β1 (SMD = -3.36; 95% CI: - 5.62, -1.09) and interleukin-6 (SMD = -1.69; 95% CI: - 3.14, -0.24). Conclusion: The present meta-analysis showed that administration of MSCs-CM improves pulmonary fibrosis. It seems that the effect of MSCs-CM was mediated by reducing collagen deposition as well as inhibiting the production of inflammatory chemokines such as TGF-β1 and interleukin 6 (IL-6). Since there is no evidence on the efficacy of MSCs-CM in large animals, further studies are needed to translate the finding to clinical studies.

Mesenchyme Stem Cell-Derived Conditioned Medium as a Potential Therapeutic Tool in Idiopathic Pulmonary Fibrosis

“…In addition, using an animal experimental model of IPF, we found that our CM reduced lung tissue production of pro-inflammatory cytokines, it had an anti-fibrotic effect capable of inhibiting inflammatory and fibrotic responses in the lung, ameliorating fibrosis, and it also was safe for the animals used [ 56 ]. Overall, the CM we used seems to exert immunomodulatory properties, it was safe for the animal model, and as mentioned earlier AD-MSCs exert similar antifibrotic properties with CM of different stem cell origin [ 55 ], which makes it a plausible candidate for further development towards a treatment for IPF. There is evidence that the CM of adipose-derived-MSCs interact with NK cells, monocytes, macrophages, and effector and regulatory T cells to shift their pro-inflammatory T helper type 1 (Th1) cytokine secretion profile to an anti-inflammatory T helper type 2 (Th2) cytokine profile [ 64 ].…”

“…Administration of MSCs-CM exerts all the beneficial effects derived from the paracrine action and secretome production from stem cell transplants, without the side effects of stem cell transplants [ 4 ]. Thus, the use of CM has been proposed as a potentially effective therapeutic strategy for the treatment of pulmonary fibrosis, and MSCs-CM has been used in experimental and clinical studies [ 55 , 56 , 57 , 58 , 59 ].…”

“…A meta-analysis of seven studies that examined in animal models the effect of MSCs-CM in pulmonary fibrosis showed that the administration of MSCs-CM significantly decreased collagen deposition in animals with pulmonary fibrosis, and reduced the score of pulmonary fibrosis. The studies were performed on rats and mice, and they use CM from marrow-derived mesenchymal stromal cells, adipose tissue-derived mesenchymal stromal cells, and amniotic-derived mesenchymal tissue cells [ 55 ]. Subgroup analysis did not reveal any differences in the positive effect of MSCs-CM, despite the animal species, the induction of pulmonary fibrosis, or the of MSCs.…”

“…Subgroup analysis did not reveal any differences in the positive effect of MSCs-CM, despite the animal species, the induction of pulmonary fibrosis, or the of MSCs. The latter finding is particularly important because adipose-derived stem cells (ADSCs) are much easier to obtain and administer than other stem cell sources and could be more easily used in future studies [ 55 ].…”

Mesenchymal Stromal Cells for the Treatment of Interstitial Lung Disease in Children: A Look from Pediatric and Pediatric Surgeon Viewpoints

“…The therapeutic strategy is mainly based on the use of corticosteroids, hydroxychloroquine, azithromycin, and supportive care; however, the efficacy is of these methods is variable. The role of MSCs as a state-of-the-art treatment has been proposed in clinical and preclinical studies [ 4 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”