title: Enhanced Homing of CXCR-4 Modified Bone Marrow-Derived Mesenchymal Stem Cells to Acute Kidney Injury Tissues by Micro-Bubble-Mediated Ultrasound Exposure.
abstract: Although the curative effects of bone marrow stromal cells (BMSCs) for acute kidney injury (AKI) have been recognized, their in vivo reparative capability is limited by the low levels of targeted homing and retention of intravenous injected cells. Stromal cell-derived factor-1 (SDF-1) plays an important role in stem cell homing and retention through interaction with its specific functional receptor, CXCR4, which is presumably related to the poor homing in AKI therapy. However, most of the functional CXCR4 chemokine receptors are lost upon in vitro culturing. Ultrasound-targeted micro-bubble destruction (UTMD) has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve BMSC homing to AKI kidneys, we isolated and cultured rat BMSCs to third passage and enhanced CXCR-4 transfection efficiency in vitro by applying UTMD and polyethylenimine. Transwell migration assay showed that the migration ability of CXCR4-modified BMSCs was nine-fold higher than controls. Then, mercuric chloride-induced AKI rats were injected with transfected BMSCs through their tail veins. We showed that enhanced homing and retention of BMSCs were observed in the CXCR-4 modified group compared with other groups at 1, 2 and 3 d post-treatment. Collectively, our data indicated that UTMD was an effective method to increase BMSCs' engraftment to AKI kidney tissues by increasing CXCR-4 expression.
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Nephropathy, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Zhongxiong
authors.initials: Z
authors.lastname: Zhuo
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Shengzheng
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Linru
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gan
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Kaibin
authors.initials: K
authors.lastname: Tan
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China. Electronic address: xqgaoyh@outlook.com.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Gao
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D005466:Fluorocarbons / Q000528:radiation effects*; D019220:High-Energy Shock Waves; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D045423:Microbubbles; D010957:Plasmids / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology*; D013010:Sonication / Q000379:methods*; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome
chemical_list: C486264:Cxcr4 protein, rat; D005466:Fluorocarbons; D019718:Receptors, CXCR4; C042852:perflutren
keywords: Acute kidney injury; Bone marrow stromal cells; CXCR-4; Homing; Microbubble; Ultrasound