Effects of mesenchymal stromal cell-conditioned media on measures of lung structure and function: a systematic review and meta-analysis of preclinical studies

Abstract

Background Lung disease is a leading cause of morbidity and mortality. A breach in the lung alveolar-epithelial barrier and impairment in lung function are hallmarks of acute and chronic pulmonary illness. This review is part two of our previous work. In part 1, we demonstrated that CdM is as effective as MSCs in modulating inflammation. Herein, we investigated the effects of mesenchymal stromal cell (MSC)-conditioned media (CdM) on (i) lung architecture/function in animal models mimicking human lung disease, and (ii) performed a head-to-head comparison of CdM to MSCs. Methods Adhering to the animal Systematic Review Centre for Laboratory animal Experimentation protocol, we conducted a search of English articles in five medical databases. Two independent investigators collected information regarding lung: alveolarization, vasculogenesis, permeability, histologic injury, compliance, and measures of right ventricular hypertrophy and right pulmonary pressure. Meta-analysis was performed to generate random effect size using standardized mean difference with 95% confidence interval. Results A total of 29 studies met inclusion. Lung diseases included bronchopulmonary dysplasia, asthma, pulmonary hypertension, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. CdM improved all measures of lung structure and function. Moreover, no statistical difference was observed in any of the lung measures between MSCs and CdM. Conclusions In this meta-analysis of animal models recapitulating human lung disease, CdM improved lung structure and function and had an effect size comparable to MSCs.

Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation

“…EXOs are nanosized structures carrying functional molecules [ 33 ], and can be considered a promising therapeutic tool for acute lung injury because they reduce inflammation and enhance tissue regeneration [ 34 , 35 , 36 ]. Similarly, MSC-derived CM has demonstrated beneficial effects on lung diseases [ 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. The use of MSC-derived products rather than direct use of MSCs can prevent all the risks associated with live-cell transplants.…”

Mesenchymal Stem Cells: Exosomes and Conditioned Media as Innovative Strategies in the Treatment of Patients With Autoimmune Diseases

“…У метааналізі 29 досліджень впливу МСК та КС-МСК на показники структури та функції легень у хворих на бронхолегеневу дисплазію, астму, легеневу гіпертензію, гострий респіраторний дистрессиндром, хронічне обструктивне захворювання легень і легеневий фіброз не спостерігалося жодної статистичної різниці у ефективності за будь-яким з показників легенів між клітинними препаратами та безклітинними кондиціонованими середовищами [39,40].…”

Cellular Therapy for the Treatment of Paediatric Respiratory Disease

“…MSC conditioned medium consists of all expressed cytokines, proteins, growth factors and EVs of the cell [36]. In a comparative study for the evaluation of MSC conditioned medium and the MSCs as a therapy both alone and in combination, comparable results for efficacy were recorded [37]. In a murine model of E. coli-induced ALI, MSC-derived conditioned medium administration led to a reduction in septal thickening, alveolar haemorrhage, alveolar infiltrates and fibrin strands determined by histological staining of the lung when compared to untreated controls [38].…”