Table 2 Experimental studies testing the efficacy of MSC-derived EVs in IRI-AKI
Type of model | Species | Intervention | Administration methods | Main findings | Reference |
|---|---|---|---|---|---|
In vitro, tubular epithelial cells | - | Human bone marrow MSC-derived EVs | Incubation in culture media | • EVs incorporated into injured cells • Downregulated miRNAs associated with apoptosis, cytoskeleton and hypoxia • Downregulated microRNAs involved in apoptosis, fibrosis, hypoxia, and cytoskeletal reorganization | Lindoso et al. 2014 [32] |
In vivo | Rat | Human bone marrow MSC-derived EVs | Intravenous | • EVs decreased tubular injury and apoptosis • Improved cell proliferation and renal function • Transferred RNA-based information to recipient cells | Gatti et al. 2011 [33] |
In vivo | Rat | Autologous bone marrow MSC-derived EVs | Intravenous | • EVs decreased tubular injury, apoptosis, and inflammation • Improved renal function | Wang et al. 2014 [34] |
In vivo | Rat | Human umbilical cord MSC-derived EVs | Intravenous | • EVs decreased renal oxidative stress • Increased renal cell proliferation, attenuated apoptosis and fibrosis, and normalized renal function | Zhang et al. 2014 [35] |
In vivo; in vitro, tubular epithelial cells | Rat | Human umbilical cord MSC-derived EVs | Intravenous; incubation in culture media | • EVs improved renal function • Decreased tubular injury, oxidative stress, apoptosis, and necrosis | Zhang et al. 2016 [36] |
In vivo | Rat | Human umbilical cord MSC-derived EVs | Intravenous | • EVs reduced apoptosis and enhanced tubular cell proliferation • Improved renal function and ameliorated tubular injury and fibrosis • Increased renal angiogenesis • Transferred proangiogenic-related VEGF and mRNAs to recipient cells | Zou et al. 2016 [37] |
In vivo; in vitro, tubular epithelial cells | Rat | Human umbilical cord MSC-derived EVs | Intravenous; incubation in culture media | • EVs upregulated proangiogenic factors • Decreased tubular cell apoptosis, collagen deposition, and fibrosis | Ju et al. 2015 [38] |
In vivo; in vitro, umbilical vein endothelial cells | Mouse | Allogenic kidney resident MSC-derived EVs | Intravenous; incubation in culture media | • EVs incorporated into endothelial cells, decreased apoptosis, and increased proliferation and tube formation • Selectively engrafted into injured cells and improved renal function • Ameliorated peritubular capillary rarefaction and improved endothelial cell proliferation | Choi et al. 2014 [39] |
In vivo | Rat | Human umbilical cord MSC-derived EVs | Intravenous | • EVs increased renal proliferation • Decreased renal inflammation, tubular and glomerular injury, vascular damage, apoptosis, and fibrosis • Preserved renal function | Zou et al. 2014 [40] |
In vivo | Rat | Allogenic adipose tissue MSC-derived EVs | Intravenous | • EVs increased renal angiogenesis and decreased inflammation, oxidative stress, apoptosis, fibrosis • Improved renal function | Lin et al. 2016 [41] |
Ex vivo model of renal ischemia, post-circulatory death and pre-transplant | Rat | Allogenic bone marrow MSC-derived EVs | Incubation in buffering solution of donated kidney | • EVs decreased global ischemic damage • Preserved cellular metabolism and viability | Gregorini et al. 2017 [42] |