An Analysis of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Preclinical Use
- 22 July 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Nano
- Vol. 14 (8), 9728-9743
- https://doi.org/10.1021/acsnano.0c01363
Abstract
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can reduce inflammation, promote healing and improve organ function thereby providing a potential ‘cell-free’ therapy. Prior to clinical translation, it is critical to synthesize existing evidence on preclinical methods and efficacy. To address these issues, we used gold standard systematic review methodology to consolidate information from all published animal studies investigating MSC-EVs as an intervention. Systematic search of MEDLINE and Embase identified 206 studies. Data was extracted in duplicate for methodology, experimental design, interventional traits, modifications and outcomes. MSC-EVs were used to treat a variety of diseases and demonstrated benefits in 97% of studies. Adverse effects were reported in only three studies; two demonstrating tumor growth. A quarter of articles modified EVs to enhance efficacy with 72% leading to markedly improved outcomes as compared to unmodified EVs. However, several key methodological concerns were evident. Only 60% of studies used nomenclature consistent with the size definitions of EVs. Ultracentrifugation (70%) and isolation kits (23%) were the most common isolation techniques despite differences in yield and purity. EVs were inconsistently dosed by protein (68%) or particle concentration (16%). Two-thirds of studies administered xenogeneic EVs suggesting immunocompatibility. Less than 25% of studies assessed EV biodistribution. Approaches for determining size, protein markers and morphology was highly heterogeneous with only 12 and 4 studies meeting the MISEV 2014 and 2018 recommendations, respectively. Knowledge gaps identified from this systematic review highlight important opportunities to improve preclinical design and methodology in the rapidly growing field of EV therapeutics.Keywords
Funding Information
- Canadian Vascular Network Scholar Award
- Ottawa Hospital Anesthesia Alternate Funds Association
- Vanier Canada Graduate Scholarship
This publication has 70 references indexed in Scilit:
- Extracellular membrane vesicles from umbilical cord blood‐derived MSC protect against ischemic acute kidney injury, a feature that is lost after inflammatory conditioningJournal of Extracellular Vesicles, 2013
- A call for transparent reporting to optimize the predictive value of preclinical researchNature, 2012
- The MSC: An Injury DrugstoreCell Stem Cell, 2011
- Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSCCell Communication and Signaling, 2011
- Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCsJournal of Translational Medicine, 2011
- FDI and spillovers in China: non-linearity and absorptive capacityJournal of Chinese Economic and Business Studies, 2011
- Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of EfficacyPLoS Biology, 2010
- Mesenchymal Stem Cell-Derived Microvesicles Protect Against Acute Tubular InjuryJournal of the American Society of Nephrology, 2009
- Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftmentBiochemical and Biophysical Research Communications, 2007