Clinical tissue transplantation confirmed vessel patency and tissue viability for 1 week. The metabolic activity of the bioartificial tissue increased continuously over time in vitro. The human endothelial cells formed a viable endothelium inside the primarily porcine extracellular matrix, expressing CD31, Flk-1, and vascular endothelium-cadherin. Cell residues were removed by additional tissue incubation with DNAse. Tissue preparation with sodium desoxycholate monohydrate solution resulted in an incomplete decellularization. To evaluate the tissue capabilities, it was implanted clinically and recovered after 1 week. The engineered tissue was characterized by (1) histology, (2) immune-histology, (3) life-dead assay, and (4) metabolic activity.
The vascular remainings were reseeded with human endothelial cells in a dynamic tissue culture. The extracellular matrix was characterized quantitatively for DNA residues and protein composition. Methods.Ī porcine small bowl segment was decellularized in a two-step procedure, preserving its vascular structures. The tissue was implanted clinically as proof of concept to evaluate vascular network thrombogenicity and tissue viability after transplantation. We developed techniques to generate a bioartificial human tissue with an innate vascularization. The lack of transplant vascularization forecloses the generation and clinical implementation of bioartificial tissues. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site ( Background. Supplementary digital content is available for this article. The authors declare no conflict of interest.ĤAddress correspondence to: Thorsten Walles, M.D., F.E.T.C.S., Department of Thoracic Surgery, Schillerhoehe Hospital, Solitudestrasse 18, D-70839 Gerlingen, Germany. performed the animal experiments and explanted the porcine jejunal segments needed for BioVaSc generation. designed and developed the computer based bioreactor system and programmed the software. performed the tissue reseeding along with J.S. and evaluated the clinical transplant function. performed the decellularization procedure, isolated the autologous cells from the tissue samples, participated in the tissue reseeding, and performed the immunohistochemistry and staining and functional characterization of the reseeded BioVaSc. conceived, designed, and oversaw all the studies, collection of results, interpretation of data, and writing the manuscript. This work was supported by Fraunhofer program MEF 600 100 72. 1 At eGenesis, we are harnessing this innovation to tackle both of the hurdles that have prevented the advancement of xenotransplantation to date and to create Human Compatible (HuCo™) organs and cells to address the transplant shortage crisis.1Fraunhofer Institute for Interfacial Engineering and Biotechnology, Department Cellsystems, Stuttgart, Germany.ĢDepartment of General Thoracic Surgery, Schillerhöhe Hospital, Gerlingen, Germany.ģDepartment of General, Visceral and Transplant Surgery, Tübingen University Hospital, Tübingen, Germany. Recent innovations in gene-editing technology enable more precise yet more feasible editing of the genome than was ever before possible. Immune-mediated incompatibilities between species leading to organ rejection.The potential risk of the transmission of viruses between species.In the past, two key hurdles have prevented successful xenotransplantation: Pigs have been identified as a good species for xenotransplantation due to their similarity to humans in terms of organ structure and physiology, in addition to the abundance of the species. Xenotransplantation is the transplantation of living organs, tissues, or cells from one species to another. Xenotransplantation is one approach that has the potential to sufficiently address the organ shortage crisis. Human donor organs may never fully meet demand. Numerous strategies to increase human donor organ supply have not closed the staggering supply-demand gap that only continues to increase.
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