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Meta-Analysis
. 2022 May 30;11(11):1797.
doi: 10.3390/cells11111797.

Stem Cell-Based Regenerative Therapy and Derived Products in COPD: A Systematic Review and Meta-Analysis

Luigino Calzetta  1 , Marina Aiello  1 , Annalisa Frizzelli  1 , Francesca Camardelli  2 , Mario Cazzola  2 , Paola Rogliani  2 , Alfredo Chetta  1
Affiliations
Meta-Analysis

Stem Cell-Based Regenerative Therapy and Derived Products in COPD: A Systematic Review and Meta-Analysis

Luigino Calzetta et al. Cells. .

Abstract

COPD is an incurable disorder, characterized by a progressive alveolar tissue destruction and defective mechanisms of repair and defense leading to emphysema. Currently, treatment for COPD is exclusively symptomatic; therefore, stem cell-based therapies represent a promising therapeutic approach to regenerate damaged structures of the respiratory system and restore lung function. The aim of this study was to provide a quantitative synthesis of the efficacy profile of stem cell-based regenerative therapies and derived products in COPD patients. A systematic review and meta-analysis was performed according to PRISMA-P. Data from 371 COPD patients were extracted from 11 studies. Active treatments elicited a strong tendency towards significance in FEV1 improvement (+71 mL 95% CI -2−145; p = 0.056) and significantly increased 6MWT (52 m 95% CI 18−87; p < 0.05) vs. baseline or control. Active treatments did not reduce the risk of hospitalization due to acute exacerbations (RR 0.77 95% CI 0.40−1.49; p > 0.05). This study suggests that stem cell-based regenerative therapies and derived products may be effective to treat COPD patients, but the current evidence comes from small clinical trials. Large and well-designed randomized controlled trials are needed to really quantify the beneficial impact of stem cell-based regenerative therapy and derived products in COPD.

Keywords: COPD; mesenchymal stem cells; meta-analysis; regenerative.

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Conflict of interest statement

L.C. has no conflict of interest to declare; M.A. has no conflict of interest to declare; A.F. has no conflict of interest to declare; F.C. has no conflict of interest to declare; M.C. has no conflict of interest to declare; P.R. has no conflict of interest to declare.; A.C. has no conflict of interest to declare.

Figures

Figure 1
Figure 1
PRISMA 2020 flow diagram for the identification of the clinical studies included in the qualitative and quantitative synthesis. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2
Figure 2
Forest plots of the impact of stem cell-based regenerative therapies vs. baseline or CTL on FEV1 (A), FVC (B), RV (C), and DLCO (D) and subgroup analysis on the MD in FEV1 (A’) and FVC (B’) reported as volume in mL. ADSC: adipose tissue-derived stem cells; BMMC: bone marrow mononuclear cells; BM-MSC: bone marrow-derived mesenchymal stem cells; CTL: control; DLCO: diffusing capacity for carbon monoxide; FEV1: forced expiratory volume in the 1st second; FVC: forced vital capacity; MD: mean difference; OBS: observational study; PBSC: peripheral blood stem cells; PL-MSC: placenta-derived mesenchymal stem cells; RCT: randomized controlled trial; RV: residual volume; SMD: standardized mean difference; UC-MSC: umbilical cord mesenchymal stem cells.
Figure 3
Figure 3
Forest plots of the impact of stem cell-based regenerative therapies vs. baseline or CTL on the risk of hospitalization due to AECOPD (A), 6MWT (B), and pCO2 (C). ADSC: adipose tissue-derived stem cells; AECOPD: acute exacerbation of COPD; BMMC: bone marrow mononuclear cells; BM-MSC: bone marrow-derived mesenchymal stem cells; COPD: chronic obstructive pulmonary disease; CTL: control; MD: mean difference; pCO2: partial pressure of carbon dioxide; PL-MSC: placenta-derived mesenchymal stem cells; RCT: randomized controlled trial; RR: relative risk; UC-MSC: umbilical cord mesenchymal stem cells; 6MWT: 6 min walking test. ** indicates p-value < 0.01.
Figure 4
Figure 4
Assessment of the risk of bias via the traffic light plot of each included RCT (A) and the weighted plot for the assessment of the overall risk of bias via the Cochrane RoB 2 tool (B) (n = 3 studies). Traffic light plot reports five risk of bias domains: D1, bias arising from the randomization process; D2, bias due to deviations from intended intervention; D3, bias due to missing outcome data; D4, bias in measurement of the outcome; D5, bias in selection of the reported result; yellow circle indicates some concerns on the risk of bias and green circle represents low risk of bias. RCT: randomized controlled trial; RoB: risk of bias [56,57,58].
Figure 5
Figure 5
Funnel plot (A,C) and graphical representation of Egger’s test (B,D) for the overall impact of stem cell-based regenerative therapies and derived products vs. baseline or CTL on FEV1 (A,B) and for the sensitivity analysis on FEV1 (C,D). CTL: control; FEV1: forced expiratory volume in the 1st second; SMD: standardized mean difference; SND: standard normal deviation.
See this image and copyright information in PMC

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