Effects of Transplantation with Marrow-Derived Mesenchymal Stem Cells Modified with Survivin on Renal Ischemia-Reperfusion Injury in Mice
3
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: To determine whether renal injury induced by ischemia-reperfusion (I/R) could be further improved by mesenchymal stem cells (MSCs) modified with survivin. Materials and Methods: Lentiviral vectors were used to introduce the survivingene into MSCs and the MSCs modified with survivin were transplanted into established mice models of renal I/R injury. Seven days later, serum creatinine (Scr) and blood urea nitrogen (BUN) were measured and the survival of MSCs was determined. Hematoxylin and eosin staining was used to assess renal pathologicalchange. The expressions of hepatocyte growth factor (HGF) and basic fibroblastgrowth factor (bFGF) in kidney tissue were detected by western blot. Results:Mice transplanted with survivin-modified MSCs demonstrated good renal function recovery with Scr and BUN decline close to normal levels and improvementof renal I/R injury repair. Additionally, the survival of transplanted MSCs modified with survivin was enhanced and the expression of HGF and bFGF in kidney tissue was increased. Conclusion: Our results demonstrated that MSCs engineeredto over-express survivin could enhance their therapeutic effect on renal I/R injury in mice, probably via the improved survival ability of MSCs and increasedproduction of protective cytokines in ischemic tissue.
Abstract
Purpose: To determine whether renal injury induced by ischemia-reperfusion (I/R) could be further improved by mesenchymal stem cells (MSCs) modified with survivin. Materials and Methods: Lentiviral vectors were used to introduce the survivingene into MSCs and the MSCs modified with survivin were transplanted into established mice models of renal I/R injury. Seven days later, serum creatinine (Scr) and blood urea nitrogen (BUN) were measured and the survival of MSCs was determined. Hematoxylin and eosin staining was used to assess renal pathologicalchange. The expressions of hepatocyte growth factor (HGF) and basic fibroblastgrowth factor (bFGF) in kidney tissue were detected by western blot. Results:Mice transplanted with survivin-modified MSCs demonstrated good renal function recovery with Scr and BUN decline close to normal levels and improvementof renal I/R injury repair. Additionally, the survival of transplanted MSCs modified with survivin was enhanced and the expression of HGF and bFGF in kidney tissue was increased. Conclusion: Our results demonstrated that MSCs engineeredto over-express survivin could enhance their therapeutic effect on renal I/R injury in mice, probably via the improved survival ability of MSCs and increasedproduction of protective cytokines in ischemic tissue.
참고문헌 (24)
- Snoeijs MG, "Acute ischemic injury to the renal microvasculature in human kidney transplantation", Am J Physiol Renal Physiol, 299, pp.F1134~F1140 (2010)
- Karkouti K, "Acute kidney injury after cardiac surgery: focus on modifiable risk factors", Circulation, 119, pp.495~502 (2009)
- Sharfuddin AA, "Pathophysiology of ischemic acute kidney injury", Nat Rev Nephrol, 7, pp.189~200 (2011)
- Chua HR, "Acute kidney injury after cardiac arrest", Resuscitation, 83, pp.721~727 (2012)
- Henry SD, "Protective effects of hypothermic ex vivo perfusion on ischemia", reperfusion injury and transplant outcomes, 2012, pp.26, 163~175
- Hu L, "Erythropoietin ameliorates renal ischemia and reperfusion injury via inhibiting tubulointerstitial inflammation", J Surg Res, 176, pp.260~266 (2012)
- Krause DS, "Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell", Cell, 105, pp.369~377 (2001)
- Nagaya N, "Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis", Am J Physiol Heart Circ Physiol, 287, pp.H2670~H2676 (2004)
- Tögel F, "Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms", Am J Physiol Renal Physiol, 289, pp.F31~F42 (2005)
- Lange C, "Administered mesenchymal stem cells enhance recovery from ischemia", reperfusion-induced acute renal failure in rats, 2005, pp.68, 1613~1617
- Duffield JS, "Kidney tubular epithelium is restored without replacement with bone marrow-derived cells during repair after ischemic injury", Kidney Int, 68, pp.1956~1961 (2005)
- Mylotte LA, "Metabolic flexibility permits mesenchymal stem cell survival in an ischemic environment", Stem Cells, 26, pp.1325~1336 (2008)
- Chen J, "Caspase inhibition by Z-VAD increases the survival of grafted bone marrow cells and improves functional outcome after MCAo in rats", J Neurol Sci, 199, pp.17~24 (2002)
- Wei L, "Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia", Neurobiol Dis, 19, pp.183~193 (2005)
- Fan L, "Transplantation with survivin-engineered mesenchymal stem cells results in better prognosis in a rat model of myocardial infarction", Eur J Heart Fail, 11, pp.1023~1030 (2009)
- Liu N, "Effects of transplantation with bone marrow-derived mesenchymal stem cells modified by Survivin on experimental stroke in rats", J Transl Med, 9, pp.105~ (2011)
- Deng W, "Adenoviral gene transfer of eNOS: high-level expression in ex vivo expanded marrow stromal cells", Am J Physiol Cell Physiol, 285, pp.C1322~C1329 (2003)
- Villanueva S, "NFAT5 is activated by hypoxia: role in ischemia and reperfusion in the rat kidney", PLoS One, 7, pp.e39665~ (2012)
- Tohill M, "Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration", Neurosci Lett, 362, pp.200~203 (2004)
- Zhao Y, "Mesenchymal stem cell transplantation improves regional cardiac remodeling following ovine infarction", Stem Cells Transl Med, 1, pp.685~695 (2012)
- Mangi AA, "Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts", Nat Med, 9, pp.1195~1201 (2003)
- Huls M, "Insights into the role of bone marrow-derived stem cells in renal repair", Kidney Blood Press Res, 31, pp.104~110 (2008)
- Chiou SK, "Survivin - an anti-apoptosis protein: its biological roles and implications for cancer and beyond", Med Sci Monit, 9, pp.PI25~PI29 (2003)
- Tögel F, "Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury", Am J Physiol Renal Physiol, 292, pp.F1626~F1635 (2007)
