Preclinical Studies of Mesenchymal Stem Cell (MSC) Administration in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis

Abstract

BackgroundIn the last two decades, mesenchymal stem cells (MSCs) have been pre-clinically utilized in the treatment of a variety of kinds of diseases including chronic obstructive pulmonary disease (COPD). The aim of the current study was to systematically review and conduct a meta-analysis on the published pre-clinical studies of MSC administration in the treatment of COPD in animal models.Methods and ResultsA systematic search of electronic databases was performed. Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3). The pooled Hedges’s g with 95% confidence intervals (95% CIs) was adopted to assess the effect size. Random effect model was used due to the heterogeneity between the studies. A total of 20 eligible studies were included in the current systematic review. The overall meta-analysis showed that MSC administration was significantly in favor of attenuating acute lung injury (Hedges’s g = -2.325 ± 0.145 with 95% CI: -2.609 ~ -2.040, P < 0.001 for mean linear intercept, MLI; Hedges’s g = -3.488 ± 0.504 with 95% CI: -4.476 ~ -2.501, P < 0.001 for TUNEL staining), stimulating lung tissue repair (Hedges’s g = 3.249 ± 0.586 with 95% CI: 2.103~ 4.394, P < 0.001) and improving lung function (Hedges’s g = 2.053 ± 0.408 with 95% CI: 1.253 ~ 2.854, P< 0.001). The mechanism of MSC therapy in COPD is through ameliorating airway inflammation (Hedges’s g = -2.956 ± 0.371 with 95% CI: -3.683 ~ -2.229, P< 0.001) and stimulating cytokine synthesis that involves lung tissue repair (Hedges’s g = 3.103 ± 0.734 with 95% CI: 1.664 ~ 4.541, P< 0.001).ConclusionThis systematic review and meta-analysis suggest a promising role for MSCs in COPD treatment. Although the COPD models may not truly mimic COPD patients, these pre-clinical studies demonstrate that MSC hold promise in the treatment of chronic lung diseases including COPD. The mechanisms of MSCs role in preclinical COPD treatment may be associated with attenuating airway inflammation as well as stimulating lung tissue repair.

A possible role of stem cells in nasal polyposis

“…Following this concept, regenerative processes of the upper and lower airways may also involve stem cells. Indeed, the current literature implies stem cells to be involved in regenerative processes in lower airways . In the lung, different populations of epithelial cells function as adult stem cells, defined by their self‐renewal properties and phenotypic changes in response to tissue damage .…”

Hypoxia changes chemotaxis behaviour of mesenchymal stem cells via HIF‐1α signalling

“…6 One critical barrier to effective MSC therapy is their insufficient homing capability to tissues of interest, especially when MSCs are infused through the vascular route. 7 Many factors contribute to the inefficient migration of these cells, among which low surface receptors' level is of high importance. 8 Some studies have highlighted that chemokine/-chemokine receptor interactions influence stem cell recruitment to the desired target, but to the best of our knowledge none of them have investigated whether hypoxia improves the migration of MSCs.…”

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“…The doses will require further adjustments as well as the mode of drug delivery. Previously other treatments like vitamin C 28 , angiotensin receptor blockade 29 , stem cells 30 have attenuated cigarette smoke-induced emphysema in animals. Many other studies suggested statins 31 to be an effective treatment.…”