Administration of BMSCs with muscone in rats with gentamicin-induced AKI improves their therapeutic efficacy.
The therapeutic action of bone marrow-derived mesenchymal stem cells (BMSCs) in acute kidney injury (AKI) has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. In this study, we provided evidence that the administration of BMSCs combined with muscone in rats with gentamicin-induced AKI intravenously, was a feasible strategy to drive BMSCs to damaged tissues and improve the BMSC-based therapeutic effect. The effect of muscone on BMSC bioactivity was analyzed in vitro and in vivo. The results indicated that muscone could promote BMSC migration and proliferation. Some secretory capacity of BMSC still could be improved in some degree. The BMSC-based therapeutic action was ameliorated by promoting the recovery of biochemical variables in urine or blood, as well as the inhibition of cell apoptosis and inflammation. In addition, the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration. Thus, our study indicated that enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI.
Department of Regeneration Medicine, School of Pharmaceutical Science, Jilin University, Changchun, P.R. China; Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, P.R. China.
Pengfei
P
Liu
Department of Regeneration Medicine, School of Pharmaceutical Science, Jilin University, Changchun, P.R. China; Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, P.R. China.
Yetong
Y
Feng
Department of Regeneration Medicine, School of Pharmaceutical Science, Jilin University, Changchun, P.R. China.
Chao
C
Dong
Department of Regeneration Medicine, School of Pharmaceutical Science, Jilin University, Changchun, P.R. China; Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, P.R. China.
Dandan
D
Yang
Department of Regeneration Medicine, School of Pharmaceutical Science, Jilin University, Changchun, P.R. China; Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, P.R. China.
Bo
B
Li
Department of Laboratory Medicine, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, P.R. China.
Xin
X
Chen
Department of Anesthesiology, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, P.R. China.
Zhongjun
Z
Zhang
Department of Regeneration Medicine, School of Pharmaceutical Science, Jilin University, Changchun, P.R. China.
Yi
Y
Wang
Department of Regeneration Medicine, School of Pharmaceutical Science, Jilin University, Changchun, P.R. China.
Yulai
Y
Zhou
Department of Anesthesiology, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, P.R. China.
Lei
L
Zhao
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000628:therapy*; D061605:Administration, Intravenous; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018946:Chemokine CCL5; D003516:Cycloparaffins / Q000008:administration & dosage / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods; D005434:Flow Cytometry; D005839:Gentamicins / Q000009:adverse effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D054387:Receptors, CXCR / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism
C501898:Ackr3 protein, rat; D018946:Chemokine CCL5; C486264:Cxcr4 protein, rat; D003516:Cycloparaffins; D017931:DNA Primers; D005839:Gentamicins; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; C031021:muscone