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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.1
- 수록면
- 417 - 426 (10page)
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Liver disease affects millions of patients each year worldwide. Decellularized biologic matrices are plausible biomedical materials for bioengineered replacement hepatic tissue. However, one of the concerns for its safe medical application is the lack of objective assessment of the immunogen within the materials and in vivo immune responses to the matrices. The purpose of this study was to produce immunogen- reduced and biocompatible matrices from porcine liver. Whole porcine livers were perfusion decellularized and cross-linked with glutaraldehyde (GA) or genipin (GP). Proteins were extracted, and the migratory response of human leukocytes toward protein extracts was examined using an in vitro migration chamber. In addition, biopsy specimens of decellularized scaffolds were implanted subcutaneously into rodents to investigate scaffold immunogenicity. Histological staining confirmed cellular clearance from pig livers, with removal of nuclei and cytoskeletal components and widespread preservation of structural extracellular molecules. Polymerase chain reaction analysis showed that galactose-alpha-1,3-galactose-beta-1,4-N-acetylglucosamine (1,3 gal), swine leukocyte antigen, and porcine endogenous retrovirus were completely removed in the matrices. Decellularization significantly reduced the migration of monocytes compared with native porcine tissue. Although the proportion of transmigrating lymphocytes was much lower, repeating the cross-linking procedure reduced the migratory response. After implantation for 4 weeks, the decellularized and native samples were degraded, and the GA-treated group demonstrated a severe inflammatory reaction; however, minimal inflammatory cell infiltration was seen in the GPtreated group during the 8-week investigation period. In conclusion, our study provided evidence that GP crosslinking could significantly reduce the immunogenicity of decellularized liver biomaterials.
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참고문헌 (26)
참고문헌 신청
Uygun BE / 2012 / Application of whole-organ tissue engineering in hepatology / Nat Rev Gastroenterol Hepatol 9:738~744
Ott HC / 2008 / Perfusion-decellularized matrix : using nature’s platform to engineer a bioartificial heart / Nat Med 14:213~221
Bao J / 2011 / Construction of a portal implantable functional tissue-engineered liver using perfusion-decellularized matrix and hepatocytes in rats / Cell Transplant 20:753~766
Uygun BE / 2010 / Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix / Nat Med 16:814~820
Crapo PM / 2011 / An overview of tissue and whole organ decellularization processes / Biomaterials 32:3233~3243
Ott HC / 2008 / Perfusion-decellularized matrix : using nature’s platform to engineer a bioartificial heart / Nat Med 14:213~221
Bao J / 2011 / Construction of a portal implantable functional tissue-engineered liver using perfusion-decellularized matrix and hepatocytes in rats / Cell Transplant 20:753~766
Uygun BE / 2010 / Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix / Nat Med 16:814~820
Crapo PM / 2011 / An overview of tissue and whole organ decellularization processes / Biomaterials 32:3233~3243
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