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Tissue Engineering and Regenerative Medicine

, Volume 15, Issue 4, pp 453–466 | Cite as

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

  • So Young Chun
  • Dae Hwan Kim
  • Jeong Shik Kim
  • Hyun Tae Kim
  • Eun Sang Yoo
  • Jae-Wook Chung
  • Yun-Sok Ha
  • Phil Hyun Song
  • Yoon Ki Joung
  • Dong Keun Han
  • Sung Kwang Chung
  • Bum Soo Kim
  • Tae Gyun Kwon
Original Article
  • 65 Downloads

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.

Keywords

Ischemia–reperfusion Renal regeneration Inflammation Apoptosis Fibrosis 

Notes

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).

Compliance with ethical standards

Conflict of interest

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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Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • So Young Chun
    • 1
  • Dae Hwan Kim
    • 2
  • Jeong Shik Kim
    • 3
  • Hyun Tae Kim
    • 4
    • 8
  • Eun Sang Yoo
    • 4
  • Jae-Wook Chung
    • 4
    • 8
  • Yun-Sok Ha
    • 4
  • Phil Hyun Song
    • 5
  • Yoon Ki Joung
    • 6
  • Dong Keun Han
    • 7
  • Sung Kwang Chung
    • 4
  • Bum Soo Kim
    • 4
  • Tae Gyun Kwon
    • 4
    • 8
  1. 1.BioMedical Research InstituteKyungpook National University HospitalDaeguSouth Korea
  2. 2.Department of Laboratory Animal Research Support TeamYeungnam University Medical CenterDaeguSouth Korea
  3. 3.Department of PathologyCentral HospitalUlsanSouth Korea
  4. 4.Department of Urology, School of MedicineKyungpook National University, Kyungpook National University HospitalDaeguSouth Korea
  5. 5.Department of Urology, College of MedicineYeungnam UniversityDaeguSouth Korea
  6. 6.Center for Biomaterials, Korea Institute of Science and TechnologySeoulSouth Korea
  7. 7.Center for Biomaterials, Biomedical Research InstituteKorea Institute of Science and TechnologySeoulSouth Korea
  8. 8.Department of UrologyKyungpook National University Chilgok HospitalDaeguSouth Korea

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