Kidney-Targeted Transplantation of Mesenchymal Stem Cells by Ultrasound-Targeted Microbubble Destruction Promotes Kidney Repair in Diabetic Nephropathy Rats

Abstract EN

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-β1, 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-β1 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.