Abstract：Objective To detect whether adiposederived mesenchymal stem cells (ADMCSs) can differentiate into renal tubular epithelial cells and be used for treatment of acute kidney injury (AKI). Methods ADMSCs were separated and cultured in vitro, and were transfected with lentivirus carrying reporter genes of firefly luciferase and monomeric red fluorescent protein (fluc-mrfp). Transfected ADMCSs （2×106） were directly injected into renal parenchyma after establishment of AKI models induced by ischemic reperfusion injury. Distribution and differentiation of ADMSCs in rats were detected by bioluminescence imaging (BLI) and immunofluorescent staining, respectively. Results ADMSCs had positive expressions of CD29 and CD90, rather than expressions of CD34, CD45 and CD31. Lentivirus transduced ADMSCs had stable expressions of mrfp and fluc reporter genes. BLI showed persistent fluorescence signal in vivo even at day 14 after ADMSCs transplantation. Immunofluorescence staining further indicated that the transplanted ADMSCs could differentiate into tubular epithelial cells. Conclusion ADMSCs in vivo can differentiate into renal tubular epithelial cells, which provides an experimental basis for more researches on ADMSCs transplantation for treatment of AKI.
LIU Rong-fu,GAO Jia-sheng,YANG Yu-feng. Differentiation of adiposederived mesenchymal stem cells to renal tubular epithelial cells[J]. CHINESE JOURNAL OF TRAUMA, 2013, 29(2): 175-179.
［1］Mehta RL, Kellum JA, Shah SV, et al. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care, 2007, 11（2）:R31.
［2］Friedericksen DV, Van der Merwe L, Hattingh TL, et al. Acute renal failure in the medical ICU still predictive of high mortality. S Afr Med J, 2009, 99（12）：873-875.
［3］Pleniceanu O, Harari-Steinberg O, Dekel B. Concise review: kidney stem/progenitor cells: differentiate, sort out, or reprogram? Stem Cells, 2010, 28（9）：1649-1660.
［4］Morigi M, Imberti B, Zoja C, et al. Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. J Am Soc Nephrol, 2004, 15(7)：1794-1804.
［5］Morigi M, Introna M, Imberti B, et al. Human bone marrow mesenchymal stem cells accelerate recovery of acute renal injury and prolong survival in mice. Stem Cells, 2008, 26（8）:2075-2082.
［7］Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng, 2001, 7（2）:211-228.
［8］Chen YT, Sun CK, Lin YC, et al. Adipose-derived mesenchymal stem cell protects kidneys against ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction. J Transl Med, 2011, 9（1）:51-68.
［9］Liu ZQ, Wang HB, Wang Y, et al. The influence of chitosan hydrogel on stem cell engraftment, survival and homing in the ischemic myocardial microenvironment. Biomaterials, 2012, 33（11）:3093-3106.
［10］Tgel F, Hu Z, Weiss K, et al. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol, 2005, 289（1）:F31-F42.
［11］Mias C, Trouche E, Seguelas MH, et al. Ex vivo pretreatment with melatonin improves survival, proangiogenic/mitogenic activity, and efficiency of mesenchymal stem cells injected into ischemic kidney. Stem Cells, 2008, 26（7）:1749-1757.
［13］Li KH, Han Q, Yan X, et al. Not a process of simple vicariousness, the differentiation of human adipose-derived mesenchymal stem cells to renal tubular epithelial cells plays an important role in acute kidney injury repairing. Stem Cells Dev, 2010, 19（8）:1267-1275.
［14］Bulte JW, Duncan ID, Frank JA. In vivo magnetic resonance tracking of magnetically labeled cells after transplantation. J Cereb Blood Flow Metab, 2002, 22（8）:899-907.
［15］Graves EE, Weissleder R, Ntziachristos V. Fluorescence molecular imaging of small animal tumor models. Curr Mol Med, 2004, 4（4）:419-430.
［16］Jenkins DE, Hornig YS, Oei Y, et al. Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice. Breast Cancer Res, 2005, 7（4）:444-454.
［17］Tögel F, Yang Y, Zhang P, et al. Bioluminescence imaging to monitor the in vivo distribution of administered mesenchymal stem cells in acute kidney injury. Am J Physiol Renal Physiol, 2008, 295（1）:F315-F321.
［18］Perin L, Sedrakyan S, Giuliani S, et al. Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis. PLoS One, 2010, 5（2）:e9357-e9373.
［19］Zeisberg M, Hanai J, Sugimoto H, et al. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med, 2003, 9（7）:964-968.
［20］Herrera MB, Bussolati B, Bruno S, et al. Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury. Kidney Int, 2007, 72（4）:430-441.
［21］Tögel F, Isaac J, Hu Z, et al. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int, 2005, 67（5）:1772-1784.
