Mesenchymal Stromal Cell‐derived Extracellular Vesicles in Preclinical Animal Models of Tumor Growth: Systematic Review and Meta‐analysis

• Published in: Stem cell reviews and reports 2022-03, Vol.18 (3), p.993-1006
• Main Authors: Bailey, Adrian J.M., Tieu, Alvin, Gupta, Manika, Slobodian, Mitchell, Shorr, Risa, Ramsay, Tim, Rodriguez, Rosendo A., Fergusson, Dean A., Lalu, Manoj M., Allan, David S.
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Bias; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Cancer; Cell Biology; Clinical trials; Disease Models, Animal; Extracellular vesicles; Extracellular Vesicles - metabolism; Hypoxia; Life Sciences; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mesenchyme; Meta-analysis; Neoplasms - metabolism; Neoplasms - therapy; Regenerative Medicine/Tissue Engineering; Special Issue on Exosomes and Microvesicles: from Stem Cell Biology to Translation in Human Diseases; Stem Cells; Systematic review; Tumor cells
• ISSN: 2629-3269; 2629-3277
• DOI: 10.1007/s12015-021-10163-5

Background Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) have been implicated in the regulation of tumor growth. Studies remain preclinical with effects ranging from inhibition of tumor growth to cancer progression. A systematic review and meta-analysis is needed to clarify the effect of MSC-EVs on tumor growth to facilitate potential translation to clinical trials. Methods A systematic search of the literature (MEDLINE, Embase, and BIOSIS databases to June 1, 2019) identified all pre-clinical controlled studies investigating the effect of MSC-EVs on tumor growth. Study selection and data extraction were performed in duplicate. Potential risk of bias was assessed using the SYRCLE tool. A random effects meta-analysis of reduction in tumor weight/volume (primary outcome) was performed. Results We identified 29 articles and 22 reported data on tumor responses that were included for meta-analysis. Studies were associated with unclear risk of bias in a large proportion of domains in accordance with the SYRCLE tool for determining risk of bias in preclinical studies. A high risk of bias was not identified in any study. MSC-EVs had a mixed response on tumor progression with some studies reporting inhibition of tumor growth and others reporting tumor progression. Overall, MSC-EVs exerted a non-significant reduction in tumor growth compared to controls (standardized mean difference (SMD) -0.80, 95 % CI -1.64 to 0.03, p = 0.06, I 2  = 87 %). Some studies reported increased tumor growth which aligned with their stated hypothesis and some interrogated mechanisms in cancer biology. EVs isolated from MSCs that overexpressed anti-tumor RNAs were associated with significant tumor reduction in meta-analysis (SMD − 2.40, 95 % CI -3.36 to -1.44, p