VEGF-modified human embryonic mesenchymal stem cell implantation enhances protection against cisplatin-induced acute kidney injury

Abstract

The implantation of mesenchymal stem cells (MSC) has been reported as a new technique to restore renal tubular structure and improve renal function in acute kidney injury (AKI). Vascular endothelial growth factor (VEGF) plays an important role in the renoprotective function of MSC. Whether upregulation of VEGF by a combination of MSC and VEGF gene transfer could enhance the protective effect of MSC in AKI is not clear. We investigated the effects of VEGF-modified human embryonic MSC (VEGF-hMSC) in healing cisplatin-injured renal tubular epithelial cells (TCMK-1) with a coculture system. We found that TCMK-1 viability declined 3 days after cisplatin pretreatment and that coculture with VEGF-hMSC enhanced cell protection via mitogenic and antiapoptotic actions. In addition, administration of VEGF-hMSC in a nude mouse model of cisplatin-induced kidney injury offered better protective effects on renal function, tubular structure, and survival as represented by increased cell proliferation, decreased cellular apoptosis, and improved peritubular capillary density. These data suggest that VEGF-modified hMSC implantation could provide advanced benefits in the protection against AKI by increasing antiapoptosis effects and improving microcirculation and cell proliferation.

N-Acetylcysteine-Pretreated Human Embryonic Mesenchymal Stem Cell Administration Protects Against Bleomycin-Induced Lung Injury

“…The survival rate on day 28 was significantly higher in the NAChMSC group (83.3%) than in either the Bleo group (40.0%) or the hMSC group (60.0%). Similar to our previous experiments with hMSCs, 26 there was no evidence of tumor formation in any of the surviving nude mice 2 months after cell injection.…”

Human embryonic mesenchymal stem cells alleviate pathologic changes of MRL/Lpr mice by regulating Th7 cell differentiation

“…No tumorigenesis was observed in previous studies using hMSC and vascular endothelial growth factor-modified hMSC to treat acute kidney injury in nude mice. 19 The safety of using hMSC in the treatment of MRL/Lpr mice was also confirmed in our study, knowing that no tumorigenesis was observed three months after hMSC grafting.…”

Atorvastatin Improves Survival of Implanted Stem Cells in a Rat Model of Renal Ischemia-Reperfusion Injury

“…To address this problem, a number of studies aimed at promoting the retention and survival of MSCs to increase the number of cells successfully engrafting in the injured kidney have been published. The main strategy utilized has involved the alteration of ‘seeds' meaning donor cells by preconditioning or genetic modification of MSCs [24,25,26]. However, these techniques do not always provide sufficient effects for the improvement of the cell survival, and further exploration is required for clinical application due to the complexity of these procedures.…”