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Extensive Loss of Islet Mass Beyond the First Day After Intraportal Human Islet Transplantation in a Mouse Model
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
2016 (engelsk)Inngår i: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 25, nr 3, s. 481-489Artikkel i tidsskrift (Fagfellevurdert) Published
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Abstract [en]

Clinical islet transplantation is characterized by a progressive deterioration of islet graft function, which renders many patients once again dependent on exogenous insulin administration within a couple of years. In this study, we aimed to investigate possible engraftment factors limiting the survival and viability of experimentally transplanted human islets beyond the first day after their transplantation to the liver. Human islets were transplanted into the liver of nude mice and characterized 1 or 30 days after transplantation by immunohistochemistry. The factors assessed were endocrine mass, cellular death, hypoxia, vascular density and amyloid formation in the transplanted islets. One day posttransplantation, necrotic cells, as well as apoptotic cells, were commonly observed. In contrast to necrotic death, apoptosis rates remained high 1 month posttransplantation, and the total islet mass was reduced by more than 50% between 1 and 30 days posttransplantation. Islet mass at 30 days posttransplantation correlated negatively to apoptotic death. Vascular density within the transplanted islets remained less than 30% of that in native human islets up to 30 days posttransplantation and was associated with prevailing hypoxia. Amyloid formation was rarely observed in the 1-day-old transplants, but was commonly observed in the 30-day-old islet transplants. We conclude that substantial islet cell death occurs beyond the immediate posttransplantation phase, particularly through apoptotic events. Concomitant low vascularization with prevailing hypoxia and progressive amyloid development was observed in the human islet grafts. Strategies to improve engraftment at the intraportal site or change of implantation site in the clinical setting are needed.

sted, utgiver, år, opplag, sider
2016. Vol. 25, nr 3, s. 481-489
Emneord [en]
Islet transplantation, Diabetes, Amyloid, Engraftment
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-294600DOI: 10.3727/096368915X688902ISI: 000372669200005PubMedID: 26264975OAI: oai:DiVA.org:uu-294600DiVA, id: diva2:931051
Forskningsfinansiär
Swedish Research CouncilSwedish Diabetes AssociationSwedish Child Diabetes FoundationNovo NordiskTilgjengelig fra: 2016-05-26 Laget: 2016-05-25 Sist oppdatert: 2020-01-17
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Liljebäck, HannaGrapensparr, LizaOlerud, JohanCarlsson, Per-Ola

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