Abstract
Human umbilical cord-derived mesenchymal stem cells (hucMSCs) are a promising tool for damaged tissues repair, especially for the kidney. However, their efficacy requires improvement. In order to optimize the clinical utility of hucMSCs, we adopted a strategy of treating hucMSCs with 20 μmol/L of resveratrol (Res-hucMSCs), applying it in a cisplatin-induced acute kidney injury model. Interestingly, we found that Res-hucMSCs exhibited a more efficient repairing effect than did hucMSCs. Resveratrol-promoted hucMSCs secreted platelet-derived growth factor-DD (PDGF-DD) into renal tubular cells resulting in downstream phosphorylation of extracellular signal-regulated kinase (ERK), which inhibited renal tubular cells apoptosis. In contrast, PDGF-DD knockdown impaired the renal protection of Res-hucMSCs. In addition, angiogenesis induced by PDGF-DD in endothelial cells was also involved in the renal protection of Res-hucMSCs. The conditioned medium of Res-hucMSCs accelerated proliferation and migration of vascular endothelial cells in vitro and CD31 was in a high-level expression in Res-hucMSCs group in vivo. Nevertheless, the angiogenesis was abrogated when Res-hucMSCs were treated with PDGF-DD siRNA. In conclusion, our findings showed that resveratrol-modified hucMSCs activated ERK pathway in renal tubular cells and promoted angiogenesis in endothelial cells via paracrine PDGF-DD, which could be a novel strategy for enhancing the therapy efficacy of hucMSCs in cisplatin-induced kidney injury.
Highlights
Acute kidney injury (AKI) is a frequent clinical syndrome, which is characterized by a sudden loss of the kidney function[1]
Our findings demonstrated that Human umbilical cord-derived mesenchymal stem cells (hucMSCs) primed with Res activated extracellular signal-regulated kinase (ERK) signal pathway in renal tubular cells and promoted angiogenesis in endothelial cells via paracrine platelet-derived growth factor-DD (PDGF-DD), which preferably inhibited renal tubular cell apoptosis
Hematoxylin and eosin (H&E) staining of kidney tissues slices revealed that treating with dimethyl sulfoxide (DMSO)-hucMSCs or Res-hucMSCs alleviated cisplatininduced kidney injury as identified by fewer necrotic renal tubules and protein casts, and Res-hucMSCs was more effective than DMSO-hucMSCs in alleviating pathological injury (Fig. 1b)
Summary
Acute kidney injury (AKI) is a frequent clinical syndrome, which is characterized by a sudden loss of the kidney function[1]. AKI is caused by a variety of factors, including surgery, hypoxia, drugs, mechanical trauma, Mesenchymal stem cells (MSCs) are a promising tool for the treatment of kidney injury[5,6]. Previous studies showed that hucMSCs can alleviate AKI or Official journal of the Cell Death Differentiation Association. Zhang et al Cell Death and Disease (2018)9:965 chronic kidney injury[8,9], the efficacy of stem cell-based therapy can be further improved. Small-molecule drugs have an important role in regulating stem cell fate and function, and facilitate the development of cell-based therapies[10]. Resveratrol (Res, 3,5,4’-trihydroxy-trans-stilbene)-modified cardiac stem cells exerted an improved impairing effect on infarcted myocardium by increasing the survival and engraftment of implanted cardiac stem cells[11]
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