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A Novel Dorsal Slit Approached Non-Ischemic Partial Nephrectomy Method for a Renal Tissue Regeneration in a Mouse Model

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

BACKGROUND:

Kidney ischemia–reperfusion (IR) via laparotomy is a conventional method for kidney surgery in a mouse model. However, IR, an invasive procedure, can cause serious acute and chronic complications through apoptotic and inflammatory pathways. To avoid these adverse responses, a Non-IR and dorsal slit approach was designed for kidney surgery.

METHODS:

Animals were divided into three groups, 1) sham-operated control; 2) IR, Kidney IR via laparotomy; and 3) Non-IR, Non-IR and dorsal slit. The effects of Non-IR method on renal surgery outcomes were verified with respect to animal viability, renal function, apoptosis, inflammation, fibrosis, renal regeneration, and systemic response using histology, immunohistochemistry, real-time polymerase chain reaction, serum chemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and Masson’s trichrome staining.

RESULTS:

The Non-IR group showed 100% viability with mild elevation of serum blood urea nitrogen and creatinine values at day 1 after surgery, whereas the IR group showed 20% viability and lethal functional abnormality. Histologically, renal tubule epithelial cell injury was evident on day 1 in the IR group, and cellular apoptosis enhanced TUNEL-positive cell number and Fas/caspase-3 and KIM-1/NGAL expression. Inflammation and fibrosis were high in the IR group, with enhanced CD4/CD8-positive T cell infiltration, inflammatory cytokine secretion, and Masson’s trichrome stain-positive cell numbers. The Non-IR group showed a suitable microenvironment for renal regeneration with enhanced host cell migration, reduced immune cell influx, and increased expression of renal differentiation-related genes and anti-inflammatory cytokines. The local renal IR influenced distal organ apoptosis and inflammation by releasing circulating pro-inflammatory cytokines.

CONCLUSION:

The Non-IR and dorsal slit method for kidney surgery in a mouse model can be an alternative surgical approach for researchers without adverse reactions such as apoptosis, inflammation, fibrosis, functional impairment, and systemic reactions.

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science and ICT (2014M3A9D3034164), (2015R1C1A1A01053509), (2016R1C1B1011180), the Ministry of Education (2015R1D1A3A03020378) and the Ministry of Trade, Industry and Energy (R0005886).

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Author notes

  1. Bum Soo Kim and Tae Gyun Kwon contributed equally to this work as co-corresponding authors.

Authors and Affiliations

  1. BioMedical Research Institute, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, South Korea

    So Young Chun

  2. Department of Laboratory Animal Research Support Team, Yeungnam University Medical Center, 170 Hyunchung-ro, Nam-gu, Daegu, 42415, South Korea

    Dae Hwan Kim

  3. Department of Pathology, Central Hospital, 480 Munsu-ro, Nam-gu, Ulsan, 44667, South Korea

    Jeong Shik Kim

  4. Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, South Korea

    Hyun Tae Kim, Eun Sang Yoo, Jae-Wook Chung, Yun-Sok Ha, Sung Kwang Chung, Bum Soo Kim & Tae Gyun Kwon

  5. Department of Urology, College of Medicine, Yeungnam University, 170 Hyunchung-ro, Nam-gu, Daegu, 42415, South Korea

    Phil Hyun Song

  6. Center for Biomaterials, Korea Institute of Science and Technology, 5 Hwarangro, Seongbuk-gu, Seoul, 02792, South Korea

    Yoon Ki Joung

  7. Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, 5 Hwarangro, Seongbuk-gu, Seoul, 02792, South Korea

    Dong Keun Han

  8. Department of Urology, Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu, Daegu, 41404, South Korea

    Hyun Tae Kim, Jae-Wook Chung & Tae Gyun Kwon

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  1. So Young Chun
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Corresponding authors

Correspondence to Bum Soo Kim or Tae Gyun Kwon.

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The authors declare that they have no conflict of interest.

Ethical statement

Animal protocol was approved by the Yeungnam University Institutional Animal Care and Use Committee (IACUC, YUMC-AEC2016-003).

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Chun, S.Y., Kim, D.H., Kim, J.S. et al. A Novel Dorsal Slit Approached Non-Ischemic Partial Nephrectomy Method for a Renal Tissue Regeneration in a Mouse Model. Tissue Eng Regen Med 15, 453–466 (2018). https://doi.org/10.1007/s13770-018-0123-0

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  • DOI: https://doi.org/10.1007/s13770-018-0123-0

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