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Hyaluronic Acid (800 kDa) Supplementation of University of Wisconsin Solution Improves Viability of Osteochondral Grafts and Reduces Matrix Metalloproteinase Expression during Cold Preservation.

ABSTRACT: Osteochondral allografting is a promising option for the treatment of large cartilage defects. However, because the cell viability of osteochondral tissues (OCTs) gradually reduces during storage at 4°C, methods for maintaining the cell viability of fresh OCTs are needed to improve transplantation outcomes. Here, we evaluated whether the supplementation of preservation solution with one of three different molecular weight forms of hyaluronic acid (HA) improved the viability of rat OCTs during long-term cold storage. The supplementation of University of Wisconsin (UW) solution with 800 kDa significantly improved the cell viability of OCT after 14 days at 4°C compared to nonsupplemented UW solution. In contrast, UW solution supplemented with either 1900 or 6000 kDa HA did not markedly improve the cell viability of the OCT. Real-time PCR analysis revealed that the levels of matrix metalloproteinases 2, 3, and 9 were significantly decreased in OCT stored in UW solution supplemented with 800 kDa HA. Although further studies in human OCT are warranted, these findings demonstrate that the use of 800 kDa HA in place of serum may be a suitable approach for the long-term preservation of osteochondral allografts designated for the repair of large cartilage defects in the clinical setting.

SUBMITTER: Yamada T

PROVIDER: S-EPMC4496492 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) solutions.Fatty liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 °Cand subjected to "ex vivo" normo-thermic perfusion (2 h; 37 °C). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography. Total free amino acid release was correlated with the activation of the ubiquitin proteasome system (UPS: measured as chymotryptic-like activity and 20S and 19S proteasome), the prevention of liver injury (transaminases), mitochondrial injury (confocal microscopy) and inflammation markers (TNF 1 alpha, high mobility group box-1 (HGMB-1) and PPAR gamma), and liver apoptosis (TUNEL assay, cytochrome c and caspase 3).Profiles of free AA (alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significantly higher prevention of proteolysis than UW (P < 0.05) after cold ischemia reperfusion. Livers conserved in IGL-1 presented more effective prevention of ATP-breakdown and more inhibition of UPS activity (measured as chymotryptic-like activity). In addition, the prevention of liver proteolysis and UPS activation correlated with the prevention of liver injury (AST/ALT) and mitochondrial damage (revealed by confocal microscopy findings) as well as with the prevention of inflammatory markers (TNF1alpha and HMGB) after reperfusion. In addition, the liver grafts preserved in IGL-1 showed a significant decrease in liver apoptosis, as shown by TUNEL assay and the reduction of cytochrome c, caspase 3 and P62 levels.Our comparison of these two preservation solutions suggests that IGL-1 helps to prevent ATP breakdown more effectively than UW and subsequently achieves a higher UPS inhibition and reduced liver proteolysis.

Project description:BackgroundThe question of whether the choice of preservation solution affects outcome after liver transplantation is still not satisfactorily answered. The purpose of this study is to examine the preservation solutions' impact on outcome after liver transplantation.MethodsA double-center retrospective study of short- and long-term results of 3134 consecutive liver transplantations with follow-up periods up to 23 years was performed applying multivariate, risk-adjusted analyses with a subset for living-donor transplants, pediatric transplants and cases with prolonged cold ischemic times. An additional focus was put on biliary complications. The primary study endpoints were short- and long-term patient survival and death-censored graft survival. Secondary study endpoints were the occurrence of post-transplant complications, the necessity of operative revisions, the length of hospital stay, and the length of intensive care unit stay.ResultsAlthough long-term graft survival appears to be increased by Histidine-Tryptophan-Ketoglutarate-use (p = 0.018), this effect could not be confirmed in risk-adjusted analysis (p = 0.641). Multivariate regression analysis revealed that 3-month mortality (p = 0.120), 3-month graft survival (p = 0.103) and long-term patient survival (p = 0.235) were not influenced by the choice of preservation solution. There was no difference in the occurrence of common complications or necessity of operative revisions after liver transplantation. This was confirmed in subgroup analyses for living donor and pediatric transplantation and cases with prolonged cold ischemic time. Analysis of the preservation solutions' impact on length of hospital (p = 0.113) and intensive care unit stay (p = 0.481) revealed no significant difference.ConclusionsUniversity of Wisconsin and Histidine-Tryptophan-Ketoglutarate solutions are clinically equivalent. Histidine-Tryptophan-Ketoglutarate solution could have an economically superior profile. The notion that the choice of preservation solution can have an impact on the onset of biliary complications after liver transplantation remains a matter of controversy.

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Hyaluronic Acid (800 kDa) Supplementation of University of Wisconsin Solution Improves Viability of Osteochondral Grafts and Reduces Matrix Metalloproteinase Expression during Cold Preservation.

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