Implantation of Dedifferentiated Fat Cells Ameliorates Habu Snake Venom-Induced Chronic Renal Dysfunction in Tenascin-C-Deficient Mice

Abstract

Background/Aims: We established dedifferentiated fat (DFAT) cells from mature adipocytes that differentiate to multiple lineages and have characteristics similar to those of mesenchymal stem cells. In this study, we evaluated the effect of implantation of DFAT cells on habu snake venom (HSV)-induced renal dysfunction in tenascin-C knockout (TC-KO) mice. Methods: Cultured DFAT cells were incubated with PDGF-BB and immunostained with anti-desmin antibody to determine mesenchymal differentiation. HSV was injected, and DFAT cells from GFP mice were implanted in TC-KO mice via the tail vein. Expression of tenascin-C, transforming growth factor-β₁ (TGF-β1), and fibronectin mRNAs in the renal cortex were evaluated by RT-PCR analysis. Results: Cultured DFAT cells showed desmin immunostaining in response to PDGF-BB.HSV injection induced glomerulosclerosis, which was significantly improved by implantation of DFAT cells. Serum BUN increased after HSV injection and was significantly decreased by implantation of DFAT cells. Tenascin-C mRNA was detected in the renal cortex in implanted mice. Expression of TGF-β1 and fibronectin mRNAs increased in the renal cortex after HSV injection, and was significantly decreased by implantation of DFAT cells. Conclusion: DFAT cells may provide a source for cell therapy for severe progressive renal disease.