Transplantation of a bioengineered tissue patch promotes uterine repair in the sheep.

Autor:	Sehic E; Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Kvinnokliniken, Blå stråket 6, SE-405 30, Sweden. mats.hellstrom@gu.se.; Department of Obstetrics and Gynecology, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Sweden., de Miguel Gómez L; Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Kvinnokliniken, Blå stråket 6, SE-405 30, Sweden. mats.hellstrom@gu.se.; Department of Obstetrics and Gynecology, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Sweden., Rabe H; Unit of Biological Function, Division Materials and Production, RISE - Research Institutes of Sweden, Box 857, SE-50115 Borås, Sweden.; Institute of Biomedicine, Department of Infectious diseases, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Sweden., Thorén E; Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Kvinnokliniken, Blå stråket 6, SE-405 30, Sweden. mats.hellstrom@gu.se.; Department of Obstetrics and Gynecology, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Sweden., Gudmundsdottir I; Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Kvinnokliniken, Blå stråket 6, SE-405 30, Sweden. mats.hellstrom@gu.se.; Department of Obstetrics and Gynecology, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Sweden., Oltean M; Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Kvinnokliniken, Blå stråket 6, SE-405 30, Sweden. mats.hellstrom@gu.se.; Department of Surgery, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45, Sweden., Akouri R; Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Kvinnokliniken, Blå stråket 6, SE-405 30, Sweden. mats.hellstrom@gu.se.; Department of Obstetrics and Gynecology, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Sweden., Brännström M; Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Kvinnokliniken, Blå stråket 6, SE-405 30, Sweden. mats.hellstrom@gu.se.; Department of Obstetrics and Gynecology, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Sweden.; Stockholm IVF-EUGIN, Hammarby allé 93, 120 63 Stockholm, Sweden., Hellström M; Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Kvinnokliniken, Blå stråket 6, SE-405 30, Sweden. mats.hellstrom@gu.se.; Department of Obstetrics and Gynecology, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Sweden.; Unit of Biological Function, Division Materials and Production, RISE - Research Institutes of Sweden, Box 857, SE-50115 Borås, Sweden.
Jazyk:	angličtina
Zdroj:	Biomaterials science [Biomater Sci] 2024 Apr 16; Vol. 12 (8), pp. 2136-2148. Date of Electronic Publication: 2024 Apr 16.
DOI:	10.1039/d3bm01912h
Abstrakt:	Innovative bioengineering strategies utilizing extracellular matrix (ECM) based scaffolds derived from decellularized tissue offer new prospects for restoring damaged uterine tissue. Despite successful fertility restoration in small animal models, the translation to larger and more clinically relevant models have not yet been assessed. Thus, our study investigated the feasibility to use a 6 cm 2 graft constructed from decellularized sheep uterine tissue, mimicking a future application to repair a uterine defect in women. Some grafts were also recellularized with fetal sheep bone marrow-derived mesenchymal stem cells (SF-MSCs). The animals were followed for six weeks post-surgery during which blood samples were collected to assess the systemic immune cell activation by fluorescence-activated cell sorting (FACS) analysis. Tissue regeneration was assessed by histology, immunohistochemistry, and gene expression analyses. There was a large intra-group variance which prompted us to implement a novel scoring system to comprehensively evaluate the regenerative outcomes. Based on the regenerative score each graft received, we focused our analysis to map potential differences that may have played a role in the success or failure of tissue repair following the transplantation therapy. Notably, three out of 15 grafts exhibited major regeneration that resembled native uterine tissue, and an additional three grafts showed substantial regenerative outcomes. For the better regenerated grafts, it was observed that the systemic T-cell subgroups were significantly different compared with the failing grafts. Hence, our data suggest that the T-cell response play an important role for determining the uterus tissue regeneration outcomes. The remarkable regeneration seen in the best-performing grafts after just six weeks following transplantation provides compelling evidence that decellularized tissue for uterine bioengineering holds great promise for clinically relevant applications.
Databáze:	MEDLINE
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