Generation and transplantation of an autologous vascularized bioartificial human tissue.
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.
Mertsching
Heike
H
Fraunhofer Institute for Interfacial Engineering and Biotechnology, Department Cellsystems, Stuttgart, Germany.
Schanz
Johanna
J
Steger
Volker
V
Schandar
Markus
M
Schenk
Martin
M
Hansmann
Jan
J
Dally
Iris
I
Friedel
Godehard
G
Walles
Thorsten
T
D000818:Animals; D021522:Bioartificial Organs; D004730:Endothelium, Vascular / Q000637:transplantation; D005109:Extracellular Matrix / Q000637:transplantation; D006801:Humans; D007583:Jejunum / Q000098:blood supply / Q000637:transplantation; D051381:Rats; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D014182:Transplantation, Autologous / Q000379:methods*