Effects of transplantation with marrow-derived mesenchymal stem cells modified with survivin on renal ischemia-reperfusion injury in mice

Yonsei Med J. 2014 Jul;55(4):1130-7. doi: 10.3349/ymj.2014.55.4.1130.

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 survivin gene 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 pathological change. The expressions of hepatocyte growth factor (HGF) and basic fibroblast growth 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 improvement of 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 engineered to over-express survivin could enhance their therapeutic effect on renal I/R injury in mice, probably via the improved survival ability of MSCs and increased production of protective cytokines in ischemic tissue.

Keywords: Marrow-derived mesenchymal stem cells; ischemia-reperfusion; survivin; transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Inhibitor of Apoptosis Proteins / therapeutic use*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mice
  • Mice, Inbred C57BL
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / therapy*
  • Repressor Proteins / therapeutic use*
  • Survivin

Substances

  • Birc5 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Repressor Proteins
  • Survivin