title: Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats.
abstract: Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MB(SDF-1)) via covalent conjugation. The characterization and bioactivity of MB(SDF-1) were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MB(SDF-1). The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 μg/mL. MB(SDF-1) remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MB(SDF-1) destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.
authors.affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Shengzheng
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Gong
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Zhongxiong
authors.initials: Z
authors.lastname: Zhuo
authors.affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Kaibin
authors.initials: K
authors.lastname: Tan
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D045423:Microbubbles; D051381:Rats
chemical_list: D054377:Chemokine CXCL12
keywords: diabetic nephropathy; homing; mesenchymal stem cell; microbubbles; stromal cell-derived factor-1; ultrasound