BACKGROUND: The lack of transplant vascularization forecloses the generation and clinical implementation of bioartificial tissues. We developed techniques to generate a bioartificial human tissue with an innate vascularization. The tissue was implanted clinically as proof of concept to evaluate vascular network thrombogenicity and tissue viability after transplantation. METHODS: A porcine small bowl segment was decellularized in a two-step procedure, preserving its vascular structures. The extracellular matrix was characterized quantitatively for DNA residues and protein composition. The vascular remainings were reseeded with human endothelial cells in a dynamic tissue culture. The engineered tissue was characterized by (1) histology, (2) immune-histology, (3) life-dead assay, and (4) metabolic activity. To evaluate the tissue capabilities, it was implanted clinically and recovered after 1 week. RESULTS: Tissue preparation with sodium desoxycholate monohydrate solution resulted in an incomplete decellularization. Cell residues were removed by additional tissue incubation with DNAse. The human endothelial cells formed a viable endothelium inside the primarily porcine extracellular matrix, expressing CD31, Flk-1, and vascular endothelium-cadherin. The metabolic activity of the bioartificial tissue increased continuously over time in vitro. Clinical tissue transplantation confirmed vessel patency and tissue viability for 1 week. CONCLUSIONS: The feasibility to bioengineer a human tissue with an innate vascularization has been shown in vitro and the clinical setting. These results may open the door for the clinical application of various sophisticated bioartificial tissue substitutes and organ replacements.
BACKGROUND: The lack of transplant vascularization forecloses the generation and clinical implementation of bioartificial tissues. We developed techniques to generate a bioartificial human tissue with an innate vascularization. The tissue was implanted clinically as proof of concept to evaluate vascular network thrombogenicity and tissue viability after transplantation. METHODS: A porcine small bowl segment was decellularized in a two-step procedure, preserving its vascular structures. The extracellular matrix was characterized quantitatively for DNA residues and protein composition. The vascular remainings were reseeded with human endothelial cells in a dynamic tissue culture. The engineered tissue was characterized by (1) histology, (2) immune-histology, (3) life-dead assay, and (4) metabolic activity. To evaluate the tissue capabilities, it was implanted clinically and recovered after 1 week. RESULTS: Tissue preparation with sodium desoxycholate monohydrate solution resulted in an incomplete decellularization. Cell residues were removed by additional tissue incubation with DNAse. The human endothelial cells formed a viable endothelium inside the primarily porcine extracellular matrix, expressing CD31, Flk-1, and vascular endothelium-cadherin. The metabolic activity of the bioartificial tissue increased continuously over time in vitro. Clinical tissue transplantation confirmed vessel patency and tissue viability for 1 week. CONCLUSIONS: The feasibility to bioengineer a human tissue with an innate vascularization has been shown in vitro and the clinical setting. These results may open the door for the clinical application of various sophisticated bioartificial tissue substitutes and organ replacements.
Authors: Sayed-Hadi Mirmalek-Sani; David C Sullivan; Cynthia Zimmerman; Thomas D Shupe; Bryon E Petersen Journal: Am J Pathol Date: 2013-06-07 Impact factor: 4.307
Authors: Bernhard J Jank; Linjie Xiong; Philipp T Moser; Jacques P Guyette; Xi Ren; Curtis L Cetrulo; David A Leonard; Leopoldo Fernandez; Shawn P Fagan; Harald C Ott Journal: Biomaterials Date: 2015-05-22 Impact factor: 12.479
Authors: Giorgia Totonelli; Panagiotis Maghsoudlou; Jonathan M Fishman; Giuseppe Orlando; Tahera Ansari; Paul Sibbons; Martin A Birchall; Agostino Pierro; Simon Eaton; Paolo De Coppi Journal: World J Gastroenterol Date: 2012-12-21 Impact factor: 5.742
Authors: Hug Aubin; Alexander Kranz; Jörn Hülsmann; Antonio Pinto; Mareike Barth; Andrey Fomin; Artur Lichtenberg; Payam Akhyari Journal: Tissue Eng Part C Methods Date: 2013-06-04 Impact factor: 3.056
Authors: Pradeep B Patil; Priti B Chougule; Vijay K Kumar; Stefan Almström; Henrik Bäckdahl; Debashish Banerjee; Gustaf Herlenius; Michael Olausson; Suchitra Sumitran-Holgersson Journal: Stem Cells Transl Med Date: 2013-03-13 Impact factor: 6.940