Mesenchymal Stem Cells: a Promising Therapeutic Tool for Acute Kidney Injury

Selim, Rehab E.; Ahmed, Hanaa H.; Abd-Allah, Somia H.; Sabry, Gilane M.; Hassan, Rasha E.; Khalil, Wagdy K. B.; Abouhashem, Nehal S.

doi:10.1007/s12010-019-02995-2

Cited by 21 publications

(20 citation statements)

References 82 publications

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“…In the past decade, the therapeutic potential of MSCs for AKI has been extensively recognized ( Humphreys and Bonventre, 2008 ). MSCs exert immunomodulation, anti-apoptotic, antioxidative, and pro-angiogenic effects mainly through endocrine and/or paracrine means ( Selim et al, 2019 ; Fazekas and Griffin, 2020 ). Extracellular vesicles (EV) are encapsulated bio-membranes that are shed by cells into extracellular milieu and contain a varied biomolecule cargo, including saccharides, proteins, lipids, and nucleic acids ( Soekmadji et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells-Derived Exosomes Ameliorate Ischemia/Reperfusion Induced Acute Kidney Injury in a Porcine Model

Huang

Cao

Cui

et al. 2022

Front. Cell Dev. Biol.

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Exosomes are membrane-enclosed vesicles secreted by cells, containing a variety of biologically active ingredients including proteins, nucleic acids and lipids. In this study, we investigated the therapeutic effects of the exosomes and underlying mechanisms in a miniature pig model of ischemia/reperfusion-induced acute kidney injury (I/R-AKI). The exosomes were extracted from cultured human umbilical cord derived mesenchymal stem cells (hUC-MSCs) and infused into a miniature pig model of I/R AKI. Our results showed that 120 min of unilateral ischemia followed by reperfusion and contralateral nephrectomy resulted in renal dysfunction, severe kidney damage, apoptosis and necroptosis. Intravenous infusion of one dose of exosomes collected from about 4 × 108 hUC-MSCs significantly improved renal function and reduced apoptosis and necroptosis. Administration of hUC-MSC exosomes also reduced the expression of some pro-inflammatory cytokines/chemokines, decreased infiltration of macrophages to the injured kidneys and suppressed the phosphorylation of nuclear factor-κB and signal transducer and activator of transcription 3, two transcriptional factors related to inflammatory regulation. Moreover, hUC-MSC exosomes could promote proliferation of renal tubular cells, angiogenesis and upregulation of Klotho and Bone Morphogenetic Protein 7, two renoprotective molecules and vascular endothelial growth factor A and its receptor. Collectively, our results suggest that injection of hUC-MSC exosomes could ameliorate I/R-AKI and accelerate renal tubular cell repair and regeneration, and that hUC-MSC exosomes may be used as a potential biological therapy for Acute kidney injury patients.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells-Derived Exosomes Ameliorate Ischemia/Reperfusion Induced Acute Kidney Injury in a Porcine Model

Huang

Cao

Cui

et al. 2022

Front. Cell Dev. Biol.

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“…The secretome is defined as the complex array of soluble molecules and extracellular vesicles (EVs) that create a microenvironment for cellular renewal 8,22 . These bioactive factors have the therapeutic functions of anti‐fibrotic, 23 angiogenic, antioxidative, mitogenic and anti‐apoptotic 24,25 . Previous studies mainly focused on the secretome of mesenchymal stem cells (MSCs).…”

Section: Introductionmentioning

confidence: 99%

Activated SOX9+ renal epithelial cells promote kidney repair through secreting factors

et al. 2023

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A broad spectrum of lethal kidney diseases involves the irreversible destruction of the tubular structures, leading to renal function loss. Following injury, a spectrum of tissue-resident epithelial stem/progenitor cells are known to be activated and then differentiate into mature renal cells to replace the damaged renal epithelium. Here, however, we reported an alternative way that tissue-resident cells could be activated to secrete multiple factors to promote organ repair. At single-cell resolution, we showed that the resident SOX9+ renal epithelial cells (RECs) could expand in the acutely injured kidney of both mouse and human. Compared to other cells, the SOX9+ RECs overexpressed much more secretion related genes, whose functions were linked to kidney repair pathways. We also obtained long-term, feeder-free cultured SOX9+ RECs from human urine and analysed their secretory profile at both transcriptional and proteomic levels. Engraftment of cultured human SOX9+ RECs or injection of its conditional medium facilitated the regeneration of renal tubular and glomerular epithelium, probably through stimulating endogenous REC self-activation and mediating crosstalk with other renal cells. We also identified S100A9 as one of the key factors in the SOX9+ REC secretome. Altogether, the abilities to extensively propagate SOX9+ RECs in culture whilst concomitantly maintaining their intrinsic secretory capacity suggest their future application in cell-free therapies and regeneration medicine.

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“…Growing evidence in recent years has revealed that MSCs have multiple biological functions, including immunomodulation, anti-in ammation, anti-apoptosis and anti-brosis [18]. Because of these characteristics, MSCs have been applied in various diseases, such as respiratory diseases [19], circulatory system disease [20], nervous system disease [21], and kidney disease [22][23][24]. However, the underlying mechanisms of these bene cial effects are not completely elucidated.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against renal injury in diabetic nephropathy through facilitating M2 macrophage polarization by targeting TRAF6

Zhang

Zheng³

et al. 2021

Preprint

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Background Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and a common cause of end-stage renal disease, but has no approved pharmacotherapy. Mesenchymal stem cells (MSCs) possess potent anti-inflammatory and immunomodulatory properties, which render them an attractive therapeutic tool for tissue damage and inflammation. Methods This study was designed to determine the protective effects and underlying mechanisms of human umbilical cord-derived MSCs (UC-MSCs) on streptozotocin-induced DN. Renal function and histological staining were used to evaluate kidney damage. RNA high-throughput sequencing on rat kidney and UCMSC-derived exosomes was used to identify the critical miRNAs. Co-cultivation of macrophage cell line and UC-MSCs-derived conditional medium was used to assess the involvement of macrophage polarization signaling. Results UC-MSC administration significantly improved renal function, reduced the local and systemic inflammatory cytokine levels, and attenuated inflammatory cell infiltration into the kidney tissue in DN rats. Moreover, UC-MSCs shifted macrophage polarization from a pro-inflammatory M1 to an antiinflammatory M2 phenotype. Mechanistically, miR-146a-5p was significantly downregulated and negatively correlated with renal injury in DN rats as determined through high-throughput RNA sequencing. Importantly, UC-MSCs-derived miR-146a-5p promoted M2 macrophage polarization by inhibiting TRAF6-STAT1 signaling pathway. Furthermore, miR-146a-5p modification in UC-MSCs enhanced the efficacy of anti-inflammation and renal function improvement. Conclusions Collectively, our findings demonstrate that UC-MSCs-derived miR-146a-5p have the potential to restore renal function in DN rats through facilitating M2 macrophage polarization by targeting TRAF6. It will pave the way for the use of UC-MSCs for therapeutic delivery of miRNAs targeted at kidney diseases.

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Mesenchymal Stem Cells: a Promising Therapeutic Tool for Acute Kidney Injury

Cited by 21 publications

References 82 publications

Mesenchymal Stem Cells-Derived Exosomes Ameliorate Ischemia/Reperfusion Induced Acute Kidney Injury in a Porcine Model

Mesenchymal Stem Cells-Derived Exosomes Ameliorate Ischemia/Reperfusion Induced Acute Kidney Injury in a Porcine Model

Activated SOX9+ renal epithelial cells promote kidney repair through secreting factors

MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against renal injury in diabetic nephropathy through facilitating M2 macrophage polarization by targeting TRAF6

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