title: [Bone marrow mesenchymal stem cell-derived exosome protects kidney against ischemia reperfusion injury in rats].
abstract: OBJECTIVE
  To explore the protective effects and mechanism of exosomes derived from bone marrow mesenchymal stem cells (BM-MSC) on ischemia reperfusion injury (IRI) in rats.
  
  
  METHODS
  Rat-MSC were isolated, cultured and identified.Exosome was extracted from BM-MSC and observed under transmission electron microscope (TEM). The expression of surface molecular marker CD63 was tested by flow cytometry. Male Sprague-Dawley rats were randomly grouped into sham-operated (Sham), ischemia reperfusion (IR), MSC-treated (IR+MSC), MSC-derived exosome-treated (IR+MSC-ex) and fibroblast-derived exosome-treated (IR+F-ex) groups. The model for ischemia reperfusion injury was constructed. The serum levels of creatinine and blood urea nitrogen (BUN) were tested in each group. The histomorphological changes in of renal tissue samples were examined by hematoxylin and eosin-stained tissue samples. Cellular apoptosis was examined by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) staining. The expression levels of proinflammatory cytokines interleukin 1β and tumor necrosis factor α were examined by reverse transcription (RT)-PCR. And the expression level of caspase-3 was examined by Western blot.
  
  
  RESULTS
  Rat BM-MSCs were successfully isolated and cultured. Dectection of surface markers revealed high expression levels of CD29 and CD44 and a low expression level of CD34. MSC differentiated successfully into osteoblasts and lipocytes after growing in osteoblast- and lipocyte-inducing media respectively. Typical appearances of exosome were observed under transmission electron microscope. CD63 was positive on flow cytometry. Compared with the IR group, the IR+MSC and IR+MSC-ex groups showed low levels of serum creatinine and BUN, mild pathological injury, decreased number of apoptotic cells and low expression of inflammatory factors and caspase-3 (IR group, 4 310 ± 616;IR+MSC group, 2 569 ± 530; IR+MSC-ex group, 3 144 ± 343, both P < 0.05).
  
  
  CONCLUSIONS
  Rat BM-MSC-derived exosome protects against ischemia reperfusion injury with decreased inflammatory response and apoptosis in rats.
authors.affiliation: Department of Urology, Fudan University Zhongshan Hospital, Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
authors.forename: Rulin
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Urology, Fudan University Zhongshan Hospital, Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Urology, Fudan University Zhongshan Hospital, Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Urology, Fudan University Zhongshan Hospital, Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
authors.forename: Long
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Urology, Fudan University Zhongshan Hospital, Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
authors.forename: Guisheng
authors.initials: G
authors.lastname: Qi
authors.affiliation: Department of Urology, Fudan University Zhongshan Hospital, Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
authors.forename: Ruiming
authors.initials: R
authors.lastname: Rong
authors.affiliation: Department of Urology, Fudan University Zhongshan Hospital, Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Urology, Fudan University Zhongshan Hospital, Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China. Email:tyzhu@fudan.edu.cn.
authors.forename: Tongyu
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001806:Blood Urea Nitrogen; D001854:Bone Marrow Cells; D053148:Caspase 3; D002454:Cell Differentiation; D003404:Creatinine; D055354:Exosomes; D007511:Ischemia; D007668:Kidney; D008297:Male; D059630:Mesenchymal Stem Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D014409:Tumor Necrosis Factor-alpha
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine; C505410:Casp3 protein, rat; D053148:Caspase 3