title: Kidney-targeted transplantation of mesenchymal stem cells by ultrasound-targeted microbubble destruction promotes kidney repair in diabetic nephropathy rats.
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.
authors.affiliation: Department of Ultrasound, Xinqiao Hospital of the Third Military Medical University, 183 Xinqiaozheng Road, Chongqing 400037, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chuan
authors.initials: C
authors.lastname: Ye
authors.forename: Gong
authors.initials: G
authors.lastname: Wang
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Gao
authors.forename: Kaibin
authors.initials: K
authors.lastname: Tan
authors.forename: Zhongxiong
authors.initials: Z
authors.lastname: Zhuo
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xia
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Peijing
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology; D002199:Capillary Permeability; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000473:pathology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D045423:Microbubbles; D010179:Pancreas / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D014465:Ultrasonics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1