PMID- 30594241 OWN - NLM STAT- MEDLINE DCOM- 20190624 LR - 20200309 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 9 IP - 1 DP - 2018 Dec 29 TI - A combination of ultrasound-targeted microbubble destruction with transplantation of bone marrow mesenchymal stem cells promotes recovery of acute liver injury. PG - 356 LID - 10.1186/s13287-018-1098-4 [doi] LID - 356 AB - BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can provide an additional source of therapeutic stem cells for regeneration of liver cells during acute liver injury (ALI). However, the insufficient hepatic homing by the transplanted BMSCs limits their applications. Ultrasound-targeted microbubble destruction (UTMD) has been reported to promote the homing of transplanted stem cells into the ischemic myocardium. In this study, we investigated whether UTMD promotes the hepatic homing of BMSCs in ALI rats and evaluated the therapeutic effect. METHODS: BMSCs were isolated from the femurs and tibias of Sprague-Dawley (SD) rats. The isolated BMSCs were stably transfected with a lentivirus expressing enhanced green fluorescent protein (EGFP) that can be visualized and quantified in vivo after transplantation. Both tumor necrosis factor alpha (TNF-alpha) and stromal cell-derived factor 1 (SDF-1) were used to verify the appropriate ultrasound parameters. The ALI rats were divided into four groups: control, BMSCs, UTMD, and UTMD + BMSCs. The protein and mRNA expression levels of SDF-1, intercellular cell adhesion molecule (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), hepatocyte growth factor (HGF), and monocyte chemotactic protein 1 (MCP-1) in the exposed livers were analyzed at 48 h after treatment. ALI recovery was determined by serum biochemical parameters and histology. RESULTS: The isolated rat BMSCs demonstrated a good proliferation potential that was both osteogenic and adipogenic in differentiation and expressed cluster of differentiation (CD) 29 and CD90, but not CD45 or CD11b/c. After BMSC and/or UTMD treatment, the number of GFP-labeled BMSCs in the UTMD + BMSCs group was significantly higher than that of the BMSCs group (9.8 +/- 2.3 vs. 5.2 +/- 1.1/per high-power field). Furthermore, the expression of GFP mRNA was performed for evaluation of the homing rate of BMSCs in injury sites as well. In addition, the expression levels of SDF-1, ICAM-1, VCAM-1, HGF, and MCP-1 were higher (p < 0.01) in UTMD+BMSCs group. The serum levels of biomarkers were significantly lower in the UTMD + BMSCs group, and the apoptotic rate of hepatocytes in the UTMD + BMSCs group was markedly lower than that of the BMSCs group (all p < 0.05). The hepatic pathology was significantly alleviated in the UTMD + BMSCs group. CONCLUSIONS: UTMD treatment efficiently induced a favorable microenvironment for cell engraftment, resulting in improvement of hepatic homing of BMSCs, which was probably mediated through upregulation of the expression of adhesion molecules and cytokines. UTMD treatment appeared to be an effective and noninvasive approach to achieve better efficacy of BMSC-based therapy for repairing a severely injured liver. FAU - Sun, Ting AU - Sun T AD - Department of Medical Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China. FAU - Gao, Feng AU - Gao F AD - Department of Medical Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China. FAU - Li, Xin AU - Li X AD - Department of Medical Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China. FAU - Cai, Yingyu AU - Cai Y AD - Department of Medical Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China. FAU - Bai, Min AU - Bai M AD - Department of Medical Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China. FAU - Li, Fan AU - Li F AD - Department of Medical Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China. medicineli@163.com. FAU - Du, Lianfang AU - Du L AD - Department of Medical Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China. lianfang_du@126.com. LA - eng GR - No. 81471666/National Natural Science Foundation of China/International GR - 81771838/Foundation for the National Institutes of Health/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181229 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 SB - IM MH - Acute Lung Injury/pathology/*therapy MH - Animals MH - Bone Marrow Cells/*metabolism MH - Mesenchymal Stem Cell Transplantation/methods MH - Mesenchymal Stem Cells/*metabolism MH - Microbubbles/*adverse effects MH - Rats MH - Rats, Sprague-Dawley MH - Ultrasonography/*methods PMC - PMC6311028 OTO - NOTNLM OT - Acute liver injury OT - Bone marrow mesenchymal stem cells OT - Microbubble OT - Stem cell transplantation OT - Ultrasound COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: In this experiment, all animal protocols were approved by the Ethics Committee of Shanghai General Hospital and regulations. Our manuscript did not involve human resources and data. CONSENT FOR PUBLICATION: All authors agreed to publish this manuscript. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/12/31 06:00 MHDA- 2019/06/25 06:00 PMCR- 2018/12/29 CRDT- 2018/12/31 06:00 PHST- 2018/07/14 00:00 [received] PHST- 2018/12/02 00:00 [accepted] PHST- 2018/10/29 00:00 [revised] PHST- 2018/12/31 06:00 [entrez] PHST- 2018/12/31 06:00 [pubmed] PHST- 2019/06/25 06:00 [medline] PHST- 2018/12/29 00:00 [pmc-release] AID - 10.1186/s13287-018-1098-4 [pii] AID - 1098 [pii] AID - 10.1186/s13287-018-1098-4 [doi] PST - epublish SO - Stem Cell Res Ther. 2018 Dec 29;9(1):356. doi: 10.1186/s13287-018-1098-4.