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Apparent Diffusion Coefficient is a Useful Biomarker for Monitoring Adipose-Derived Mesenchymal Stem Cell Therapy of Renal Ischemic-Reperfusion Injury

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Abstract

Purpose

This study aimed to investigate the potential of apparent diffusion coefficient (ADC) for monitoring adipose-derived mesenchymal stem cell (ADMSC) therapy of renal ischemic-reperfusion injury (IRI).

Procedures

After baseline magnetic resonance imaging (MRI), 36 Sprague-Dawley rats with bilateral renal IRI were divided equally as groups 1, 2, and 3 (non-treated rats) and groups 4, 5, and 6 (ADMSC-treated rats, with 2 million ADMSCs injected via the tail vein at 6 h after IRI). Groups 1 and 4, 2 and 5, and 3 and 6 were euthanized at days 1, 3, and 7, respectively, after renal MRI. The ratios of ADC at different time points to baseline values in the cortex, outer, and inner stripes of outer medulla (OSOM/ISOM), assessments of monocyte chemoattractant protein-1 (MCP-1), CD68+ cells, tubular cast formation, and degree of fibrosis in three zones over time were compared between the non-treated and ADMSC-treated rats.

Results

Among three zones, the differences in cortical ADC and immunohistochemical changes between the non-treated and ADMSC-treated IRI rats over time were less obvious. Compared with the non-treated rats, the ADMSC-treated rats exhibited significantly higher ADC ratios of OSOM and ISOM at days 1 and 3 corresponding to significantly less MCP-1 staining, CD68+ cells, and tubular casts. From day 3 to day 7, coupling with the decrement of MCP-1 and CD68+ cells in IRI kidneys, the effect of cell density on ADC declined. By day 7, the ADMSC-treated rats showed significantly higher ADC ratios of ISOM than the non-treated IRI rats, indicating better recovery, which could be related to significantly fewer tubular casts and marked amelioration of fibrosis.

Conclusions

We suggest ADC is a useful in vivo biomarker for monitoring ADMSC therapy of renal IRI.

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Funding

This study was funded by the Ministry of Science and Technology, Taiwan (grant number MOST 103-2314-B-182A-066-MY3).

Author information

Authors and Affiliations

  1. Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Kaohsiung, Niao-Sung District, 833, Taiwan

    Sheung-Fat Ko, Chen-Chang Lee, Chung-Cheng Huang, Shu-Hang Ng & Yi-Ling Chen

  2. Department of Cardiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan

    Hon-Kan Yip

  3. Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan

    Hon-Kan Yip & Chia-Hao Su

  4. Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan

    Chia-Chang Lee

  5. Department of Biostatistics Consulting Center and Department of Public Health, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan

    Min-Chi Chen

Authors
  1. Sheung-Fat Ko
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  2. Hon-Kan Yip
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  3. Chen-Chang Lee
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  9. Min-Chi Chen
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Corresponding author

Correspondence to Sheung-Fat Ko.

Ethics declarations

The Institutional Committee on Animal Care, Use and Research approved the experiment (IACUC number: 2013110102). All applicable institutional and/or national guidelines for the care and use of animals were followed.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Ko, SF., Yip, HK., Lee, CC. et al. Apparent Diffusion Coefficient is a Useful Biomarker for Monitoring Adipose-Derived Mesenchymal Stem Cell Therapy of Renal Ischemic-Reperfusion Injury. Mol Imaging Biol 20, 750–760 (2018). https://doi.org/10.1007/s11307-018-1184-0

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  • DOI: https://doi.org/10.1007/s11307-018-1184-0

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