Acute kidney injury (AKI) causes a lot of harm to human health but is treated by only supportive therapy in most cases. Recent evidence shows that mesenchymal stem cells (MSCs) benefit kidney regeneration through releasing paracrine factors and extracellular vesicles (EVs) to the recipient kidney cells and are considered to be promising cellular therapy for AKI. To develop more efficient, precise therapies for AKI, we review the therapeutic mechanism of MSCs and MSC-derived EVs in AKI and look for a better understanding of molecular signaling and cellular communication between donor MSCs and recipient kidney cells. We also review recent clinical trials of MSC-EVs in AKI. This review summarizes the molecular mechanisms of MSCs’ therapeutic effects on kidney regeneration, expecting to comprehensively facilitate future clinical application for treating AKI.
Histology | Authors/Year Reference | EV Sources | EV Types | Experimental Model | Species | EV Factors | Molecular Response | Functional Modulation |
---|---|---|---|---|---|---|---|---|
Acute Tubular Injury | Herrera et al., 2007 [17] | BM-MSCs | NM | In vitro/in vivo, glycerol-induced AKI | Mouse | NM | ↑CD44 and hyaluronic acid (major ligand of CD44) interactions | ↑exogenous MSC migration and homing |
Gatti et al., 2011 [43] | BM-MSCs | MVs | In vivo, I/R induced acute tubular injury | Rat | NM | NM | ↓tubular cell apoptosis, ↑TEC proliferation |
|
Bruno et al., 2012 [46] | BM-MSCs | MVs | In vitro/in vivo, cisplatin-induced acute tubular injury | Mouse | Human POLR2E mRNA | ↑anti-apoptotic genes, Bcl-xL, Bcl2, and BIRC8, ↓apoptosis genes, Casp1, Casp8, and LTA |
↑renal function, morphology, and survival | |
Mb et al., 2014 [33] | hLSCs | NM | In vitro/in vivo, intra-muscle glycerol induced AKI | Mouse | NM | ↑PCNA expression | ↑tubular cell proliferation, ↑renal function, ↑morphology |
|
Chen et al., 2017 [45] | hWJMSCs | MVs | In vitro/in vivo, I/R-induced renal fibrosis | Rat | NM | ↑ERK1/2 signaling ↓EMT–related protein, TGF-β1 ↑cell cycle-related proteins, CDK 1 and CyclinB1 |
↑proliferation, ↓apoptosis, ↓collagen deposition, ↑cells in G2/M cell cycle, ↓fibrosis, ↓EMT |
|
Ranghino et al., 2017 [44] | Gl-MSCs T-CD133+ cells |
Gl-MSC-EVs T-CD133+-EVs |
In vivo, I/R induced acute tubular injury | Mouse | 62 group of miRNAs | NM | ↑TEC proliferation | |
Overath et al., 2016 [47] | ADSC-pCM | pCM | In vitro/in vivo, cisplatin-induced acute tubular injury | Mouse | 64 expressed proteins | ↓inflammatory cytokines, IL-1β, IL-6 | ↑ survival ↓ serum Cr and N-GAL |
|
Acute Glomerular Injury | Tsuda et al., 2010 [50] | FM-MSCs | NM | In vitro/in vivo, anti-Thy1 nephritis | rats | NM | ↓TNF and MCP-1 through a PGE2-dependent mechanism. | ↓Proteinuria ↓mesangial matrix/cell proliferation, ↓glomerular monocyte/macrophage infiltration, |
Zoja et al., 2012 [51] | BM-MSCs | NM | In vitro/in vivo, Adriamycin-induced crescentic nephritis | rats | NM | ↑VEGF expression ↑nephrin and CD2AP |
↓monocyte infiltration, ↓podocyte apoptosis, ↓microvascular rarefaction |
|
Iseri et al., 2016 [52] | hMSC-CM | CM | In vitro/in vivo, anti-glomerular basement membrane nephritis | rats | NM | ↓proinflammatory cytokines TNF-α, IL-1-β, MCP-1, and IL-6 | ↑M2 macrophage polarization, ↓proteinuria and crescent formation |
This entry is adapted from the peer-reviewed paper 10.3390/ijms222111406