Tissue Eng Regen Med.  2018 Aug;15(4):381-392. 10.1007/s13770-018-0120-3.

In Vivo Validation Model of a Novel Anti-Inflammatory Scaffold in Interleukin-10 Knockout Mouse

Affiliations
  • 1Biomedical Research Institute, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 41944, South Korea.
  • 2Department of Internal Medicine, Yeungnam University College of Medicine, 170 Hyunchung-ro, Nam-gu, Daegu 42415, South Korea. jbi@med.yu.ac.kr
  • 3Department of Biomedical Science, CHA University, 335 Pangyoro, Seongnam-si, Gyeonggi 13488, South Korea.
  • 4Department of Pathology, Central Hospital, 480 Munsu-ro, Nam-gu, Ulsan 44667, South Korea.
  • 5Department of Laboratory Animal Research Support Team, Yeungnam University Hospital, 170 Hyunchung-ro, Nam-gu, Daegu 42415, South Korea.
  • 6Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 41944, South Korea. tgkwon@knu.ac.kr
  • 7Department of Urology, Kyungpook National University Chilgok Hospital, 807 Hogukro, Bukgu, Daegu 41404, South Korea.

Abstract

BACKGROUND
We fabricated anti-inflammatory scaffold using Mg(OH)2-incorporated polylactic acid-polyglycolic acid copolymer (MH-PLGA). To demonstrate the anti-inflammatory effects of the MH-PLGA scaffold, an animal model should be sensitive to inflammatory responses. The interleukin-10 knockout (IL-10 KO) mouse is a widely used bowel disease model for evaluating inflammatory responses, however, few studies have evaluated this mouse for the anti-inflammatory scaffold.
METHODS
To compare the sensitivity of the inflammatory reaction, the PLGA scaffold was implanted into IL-10 KO and C57BL/6 mouse kidneys. Morphology, histology, immunohistochemistry, and gene expression analyses were carried out at weeks 1, 4, 8, and 12. The anti-inflammatory effect and renal regeneration potency of the MH-PLGA scaffold was also compared to those of PLGA in IL-10 KO mice.
RESULTS
The PLGA scaffold-implanted IL-10 KO mice showed kidneys relatively shrunken by fibrosis, significantly increased inflammatory cell infiltration, high levels of acidic debris residue, more frequent CD8-, C-reactive protein-, and ectodysplasin A-positive cells, and higher expression of pro-inflammatory and fibrotic factors compared to the control group. The MH-PLGA scaffold group showed lower expression of pro-inflammatory and fibrotic factors, low immune cell infiltration, and significantly higher expression of anti-inflammatory factors and renal differentiation related genes compared to the PLGA scaffold group.
CONCLUSION
These results indicate that the MH-PLGA scaffold had anti-inflammatory effects and high renal regeneration potency. Therefore, IL-10 KO mice are a suitable animal model for in vivo validation of novel anti-inflammatory scaffolds.

Keyword

IL-10 KO mice; Anti-inflammatory scaffold; Mg(OH)â‚‚; Renal regeneration; Fibrosis

MeSH Terms

Animals
Ectodysplasins
Fibrosis
Gene Expression
Immunohistochemistry
Interleukin-10*
Kidney
Mice
Mice, Knockout*
Models, Animal
Regeneration
Ectodysplasins
Interleukin-10
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