Kidney-targeted transplantation of mesenchymal stem cells by ultrasound-targeted microbubble destruction promotes kidney repair in diabetic nephropathy rats

Biomed Res Int. 2013;2013:526367. doi: 10.1155/2013/526367. Epub 2013 May 27.

Abstract

We test the hypothesis that ultrasound-targeted microbubble destruction (UTMD) technique increases the renoprotective effect of kidney-targeted transplantation of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in diabetic nephropathy (DN) rats. Diabetes was induced by streptozotocin injection (60 mg/Kg, intraperitoneally) in Sprague-Dawley rats. MSCs were administered alone or in combination with UTMD to DN rats at 4 weeks after diabetes onset. Random blood glucose concentrations were measured at 1, 2, 4, and 8 weeks, and plasma insulin levels, urinary albumin excretion rate (UAER) values, the structures of pancreas and kidney, the expressions of TGF- β 1, synaptopodin, and IL-10 were assessed at 8 weeks after MSCs transplantation. MSCs transplantation decreased blood glucose concentrations and attenuated pancreatic islets/ β cells damage. The permeability of renal interstitial capillaries and VCAM-1 expression increased after UTMD, which enhanced homing and retention of MSCs to kidneys. MSCs transplantation together with UTMD prevented renal damage and decreased UAER values by inhibiting TGF- β 1 expression and upregulating synaptopodin and IL-10 expression. We conclude that MSCs transplantation reverts hyperglycemia; UTMD technique noninvasively increases the homing of MSCs to kidneys and promotes renal repair in DN rats. This noninvasive cell delivery method may be feasible and efficient as a novel approach for personal MSCs therapy to diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Blotting, Western
  • Bone Marrow Cells / cytology
  • Capillary Permeability
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / pathology*
  • Diabetic Nephropathies / therapy*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation
  • Immunohistochemistry
  • Insulin / blood
  • Kidney / pathology*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Microbubbles*
  • Pancreas / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Staining and Labeling
  • Ultrasonics*
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Blood Glucose
  • Insulin
  • RNA, Messenger
  • Vascular Cell Adhesion Molecule-1