Enhanced renoprotective effect of HIF-1α modified human adipose-derived stem cells on cisplatin-induced acute kidney injury in vivo

Abstract

Current therapeutic options for acute kidney injury (AKI) are limited to the use of supportive measures and dialysis. A recent approach that has sparked great interest and gained enormous popularity is the implantation of stem cells to repair acutely damaged kidney organ. Hypoxia inducible factor-1α (HIF-1α) is effective in protecting the kidney from ischemia and nephrotoxicity. In this study, we investigated whether HIF-1α-modified adipose-derived stem cells (ASCs) had an enhanced protective effect on cisplatin-induced kidney injury in vivo. Cisplatin-induced AKI was established in nude mice. Our study demonstrated that HIF-1α-modified ASCs obviously promoted the recovery of renal function, ameliorated the extent of histologic injury and reduced renal apoptosis and inflammation, but HIF-1α-modified ASCs homed to kidney tissues at very low levels after transplantation. In addition, we also found that HIF-1α-modified ASCs significantly increased HO-1 expression in cisplatin-induced AKI in vivo. Thus, our study indicated HIF-1α-modified ASCs implantation could provide advanced benefits in the protection again AKI, which will contribute to developing a new therapeutic strategy for the treatment of AKI.

Figure 1. Renal function and histopathological analysis.

(a) The change of blood urea nitrogen (BUN). (b) The level of serum creatinine (Scr). (c) H&E staining of kidney tissues. (d) Tubular damage scores. * P < 0.05 compared with other groups. Scale bar: 100 μm.

Figure 2. Evaluation of cellular apoptosis in kidney tissues.

(a) TUNEL staining. (b) Quantification of apoptotic cells. * P < 0.05 compared with other groups, # P < 0.05 compared with EV-hASCs group. Scale bar: 100 μm.

Figure 3. Expression of inflammatory cytokines in kidney tissues.

(a) Immunohistochemical staining of RANTES, TNF-α and IL-10 in renal tissues. (b) Histological scores. * P < 0.05 compared with other groups, # P < 0.05 compared with EV-hASCs group, Δ P < 0.05 compared with EV-hASCs and HIF-1α-hASCs groups, Scale bar: 100 μm.

Figure 4. Distribution of GFP-labeled-hASCs in renal tissues under fluorescence microscope.

Scale bar: 200 μm.

Figure 5. Analysis of HO-1 expression.

(a) The expression of HO-1mRNA was tested by RT-PCR. * P < 0.05 compared with the model group, # P < 0.05 compared with EV-hASCs group. (b) The expression of HO-1 protein was examined by immunohistology. Scale bar: 200 μm.