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Exposure of von Willebrand Factor on Isolated Hepatocytes Promotes Tethering of Platelets to the Cell Surface
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
Katholieke Univ Leuven, IRF Life Sci, Lab Thrombosis Res, Campus Kulak Kortrijk, Kortrijk, Belgium.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
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2019 (Engelska)Ingår i: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 103, nr 8, s. 1630-1638Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background. Hepatocyte transplantation (Hctx) is a potentially attractive method for the treatment of acute liver failure and liver-based metabolic disorders. Unfortunately, the procedure is hampered by the instant blood-mediated inflammatory reaction (IBMIR), a thromboinflammatory response elicited by the vascular innate immune system, causing activation of the coagulation and complement systems and clearance of transplanted cells. Observations have also revealed platelets adhered to the surface of the hepatocytes (Hc). To establish Hctx as a clinical treatment, all factors that trigger IBMIR need to be identified and controlled. This work explores the expression of von Willebrand factor (VWF) on isolated Hc resulting in tethering of platelets. Methods. VWF on Hc was studied by flow cytometry, confocal microscopy, immunoblot, and real-time polymerase chain reaction. Interaction between Hc and platelets was studied in a Chandler loop model. Adhesion of platelets to the hepatocyte surface was demonstrated by flow cytometry and confocal microscopy. Results. Isolated Hc constitutively express VWF on their cell surface and mRNA for VWF was found in the cells. Hc and platelets, independently of coagulation formed complexes, were shown by antibody blocking studies to be dependent on hepatocyte-associated VWF and platelet-bound glycoprotein Ib alpha. Conclusions. VWF on isolated Hc causes, in contact with blood, adhesion of platelets, which thereby forms an ideal surface for coagulation. This phenomenon needs to be considered in hepatocyte-based reconstitution therapy and possibly even in other settings of cell transplantation.

Ort, förlag, år, upplaga, sidor
LIPPINCOTT WILLIAMS & WILKINS , 2019. Vol. 103, nr 8, s. 1630-1638
Nationell ämneskategori
Hematologi
Identifikatorer
URN: urn:nbn:se:uu:diva-393629DOI: 10.1097/TP.0000000000002707ISI: 000480691100024PubMedID: 30896677OAI: oai:DiVA.org:uu-393629DiVA, id: diva2:1354809
Tillgänglig från: 2019-09-26 Skapad: 2019-09-26 Senast uppdaterad: 2019-09-26Bibliografiskt granskad

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Gustafson, Elisabet K.Hamad, Osama A.Barbu, Andreea RNilsson, Bo

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Gustafson, Elisabet K.Hamad, Osama A.Barbu, Andreea RNilsson, Bo
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Barnkirurgisk forskningKlinisk immunologiInstitutionen för immunologi, genetik och patologiScience for Life Laboratory, SciLifeLab
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