Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Kidney Injury / chemically induced
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Acute Kidney Injury / therapy*
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Administration, Intravenous
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Analysis of Variance
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Animals
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Apoptosis / physiology
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Blotting, Western
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Chemokine CCL5
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Cycloparaffins / administration & dosage
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Cycloparaffins / pharmacology*
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DNA Primers / genetics
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Drug Delivery Systems / methods
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Flow Cytometry
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Gentamicins / adverse effects
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Immunohistochemistry
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In Situ Nick-End Labeling
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Mesenchymal Stem Cell Transplantation / methods*
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Rats
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Real-Time Polymerase Chain Reaction
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Receptors, CXCR / metabolism
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Receptors, CXCR4 / metabolism
Substances
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Ackr3 protein, rat
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Chemokine CCL5
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Cxcr4 protein, rat
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Cycloparaffins
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DNA Primers
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Gentamicins
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Receptors, CXCR
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Receptors, CXCR4
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muscone
Grants and funding
This study was supported by the grants from the Basic Research Project of Knowledge Innovation Program of Shenzhen City (No. 201404163000377), Graduate Innovation Fund of Jilin University, the Science and Technology Project of Shenzhen City (No. 200702120, 200602035), the Scientific Research of Health Department of Jilin Province (No. 2009Z043) and Science and Technology Development Project of Jilin Province (No. 20120955). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.