| 1. |
- Håkansson, Joakim, 1975, et al.
(author)
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Individualized tissue-engineered veins as vascular grafts: A proof of concept study in pig
- 2021
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In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 15:10, s. 818-830
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Journal article (peer-reviewed)abstract
- Personalized tissue engineered vascular grafts are a promising advanced therapy medicinal product alternative to autologous or synthetic vascular grafts utilized in blood vessel bypass or replacement surgery. We hypothesized that an individualized tissue engineered vein (P-TEV) would make the body recognize the transplanted blood vessel as autologous, decrease the risk of rejection and thereby avoid lifelong treatment with immune suppressant medication as is standard with allogenic organ transplantation. To individualize blood vessels, we decellularized vena cava from six deceased donor pigs and tested them for cellular removal and histological integrity. A solution with peripheral blood from the recipient pigs was used for individualized reconditioning in a perfusion bioreactor for seven days prior to transplantation. To evaluate safety and functionality of the individualized vascular graft in vivo, we transplanted reconditioned porcine vena cava into six pigs and analyzed histology and patency of the graft at different time points, with three pigs at the final endpoint 4-5 weeks after surgery. Our results showed that the P-TEV was fully patent in all animals, did not induce any occlusion or stenosis formation and we did not find any signs of rejection. The P-TEV showed rapid recellularization in vivo with the luminal surface covered with endothelial cells. In summary, the results indicate that P-TEV is functional and have potential for use as clinical transplant grafts.
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| 2. |
- Jenndahl, L., et al.
(author)
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Personalized tissue-engineered arteries as vascular graft transplants : A safety study in sheep
- 2022
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In: Regenerative Therapy. - : Japanese Society of Regenerative Medicine. - 2352-3204. ; 21, s. 331-341
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Journal article (peer-reviewed)abstract
- Patients with cardiovascular disease often need replacement or bypass of a diseased blood vessel. With disadvantages of both autologous blood vessels and synthetic grafts, tissue engineering is emerging as a promising alternative of advanced therapy medicinal products for individualized blood vessels. By reconditioning of a decellularized blood vessel with the recipient's own peripheral blood, we have been able to prevent rejection without using immunosuppressants and prime grafts for efficient recellularization in vivo. Recently, decellularized veins reconditioned with autologous peripheral blood were shown to be safe and functional in a porcine in vivo study as a potential alternative for vein grafting. In this study, personalized tissue engineered arteries (P-TEA) were developed using the same methodology and evaluated for safety in a sheep in vivo model of carotid artery transplantation. Five personalized arteries were transplanted to carotid arteries and analyzed for safety and patency as well as with histology after four months in vivo. All grafts were fully patent without any occlusion or stenosis. The tissue was well cellularized with a continuous endothelial cell layer covering the luminal surface, revascularized adventitia with capillaries and no sign of rejection or infection. In summary, the results indicate that P-TEA is safe to use and has potential as clinical grafts.
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| 3. |
- Lebens, Michael, 1956, et al.
(author)
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Construction and preclinical evaluation of mmCT, a novel mutant cholera toxin adjuvant that can be efficiently produced in genetically manipulated Vibrio cholerae
- 2016
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In: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 34:18, s. 2121-2128
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Journal article (peer-reviewed)abstract
- There is an urgent need for new adjuvants that are effective with mucosally administered vaccines. Cholera toxin (CT) is the most powerful known mucosal adjuvant but is much too toxic for human use. In an effort to develop a useful mucosal adjuvant we have generated a novel non-toxic mutant CT molecule that retains much of the adjuvant activity of native CT. This was achieved by making the enzymatically active A subunit (CTA) recalcitrant to the site-specific proteolytic cleavage ("nicking") required for toxicity, which was found to require mutations not only in the two residues rendering the molecule resistant to trypsin but also in neighboring sites protecting against cleavage by Vibrio cholerae proteases. This multiple-mutated CT (mmCT) adjuvant protein could be efficiently produced in and purified from the extracellular medium of CT-deleted V. cholerae. The mmCT completely lacked detectable enterotoxicity in an infant mouse model and had >1000-fold reduced cAMP inducing activity compared to native CT in a sensitive mammalian target cell system. It nonetheless proved to have potent adjuvant activity on mucosal and systemic antibody as well as cellular immune responses to mucosally co-administered antigens including oral cholera and intranasal influenza vaccines. We conclude that mmCT is an attractive novel non-toxic mucosal adjuvant for enhancing immune responses to co-administered mucosal vaccines
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