Implanted subcutaneous versus intraperitoneal bioscaffold seeded with hepatocyte-like cells: functional evaluation

Abstract

Background and objectives The 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. Methods After 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. Results Serum 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. Conclusion Implantation 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.

Prospects for fertility preservation: the ovarian organ function reconstruction techniques for oogenesis, growth and maturation in vitro

“…The decellularized ovarian extracellular matrix is another natural matrix obtained by removing the cellular components of the natural ovary and can highly mimic the natural ovary in vivo, allowing for cell adhesion and growth. Decellularized tissues have been applied in the liver (Fares et al, 2021), lung (Dabaghi et al, 2021), and heart (Ercan et al, 2021). Laronda et al implanted isolated mouse follicles into decellularized bovine ovarian scaffolds and transplanted them into immunocompetent normal ovariectomized mice.…”

Artificial Ovary for Young Female Breast Cancer Patients

“…Decellularized ovarian extracellular matrix is another natural matrix, obtained by removing the cellular components from the natural ovary, which can highly mimic the natural ovary in vivo allow cells to adhere and grow. Decellularized tissue has been tested in the liver ( 69 ), lung ( 70 ), and heart ( 71 ). Nevertheless, xenotransplantation may induce the immune reaction in the human body and should be paying more attention to further clinical application.…”