Abstract
Background and objectivesThe X-linked bleeding disorder, hemophilia A, is caused by defective production of factor VIII (FVIII). Hemophilic patients require regular FVIII infusions. Recombinant factor replacement poses the safest line of therapy. However, its main drawbacks are high expenses and the higher liability for formation of inhibitors. Recent studies confirmed the ability of bone marrow-derived stem cells to secrete FVIII. This study aims to generate bioscaffold from decellularized liver and subsequently seed it with trans-differentiated human stem cells into hepatic-like cells. This scaffold can then be implanted intraperitoneally or subcutaneously to provide FVIII.MethodsAfter generation of the bioscaffold, seeding of discoid scaffolds with trans-differentiated human hepatocyte-like cells was performed. Then, the generated organoid was implanted into peritoneal cavity or subcutaneous tissue of experimental rats.ResultsSerum human FVIII was significantly increased in rats subjected to subcutaneous implantation compared intraperitoneal implantation. Immunostaining for detecting Cytokeratin 19 and human anti-globulin confirmed the presence of mature human hepatocytes that were significantly increased in subcutaneous implanted scaffold compared to the intraperitoneal one.ConclusionImplantation of decellularized bioscaffold seeded with trans-differentiated stem cells in rats was successful to establish production of FVIII. Subcutaneous implantation showed higher FVIII levels than intraperitoneal implantation.
Highlights
Hemophilia is an x-linked inherited disease caused by deficiency of clotting factors VIII (Hemophilia A) or IX (Hemophilia B)
Implantation of decellularized bioscaffold seeded with trans-differentiated stem cells in rats was successful to establish production of factor VIII (FVIII)
Serum level of HF VIII was significantly increased in rats subjected to subcutaneous compared to animals received bioscaffold by intraperitoneal implantation (Fig. 2)
Summary
Hemophilia is an x-linked inherited disease caused by deficiency of clotting factors VIII (Hemophilia A) or IX (Hemophilia B). The most serious complication of replacement therapy in hemophilia is antibody production [5]. These antibodies are polyclonal high-affinity immunoglobulin G directed against the factor VIII protein leading to an increase in the management cost, morbidity and mortality [6]. The X-linked bleeding disorder, hemophilia A, is caused by defective production of factor VIII (FVIII). This study aims to generate bioscaffold from decellularized liver and subsequently seed it with trans-differentiated human stem cells into hepatic-like cells. This scaffold can be implanted intraperitoneally or subcutaneously to provide FVIII
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
