First Human use of an Allogeneic Tissue Engineered Vascular Graft: A first-in-human study to test the feasibility of an allogeneic tissue-engineered vascular graft
Presenter: Todd N. McAllister, Novato, Calif.
• Dr. Timothy J Gardner
• Dr. Elliott Antman: Chairman
• Dr. Robert Harrington
• Dr. Donna Arnett
• Dr. Eric R Bates
• Dr. Conville BrownFrank Sellke
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First Human Use of an Allogeneic Tissue Engineered Vascular Graft
Todd N. McAllister, Cytograft/St. Joseph’s Translational Res Inst, Novato, CA; Wojciech Wystrychowski, Medical UNiversity of Silesia, Katowice, Poland; Lech Cierpka, Krzysztof Zagalski, Medical Univ of Silesia, Katowice, Poland; Sergio A. Garrido, Fleni Hosp, Buenos Aires, Argentina; Samuel Radochonski, Nathalie Dusserre, Cytograft, Novato, CA; Nicolas L’Heureux, Cytograft/St. Joseph’s Translational Res Inst, Novato, CA
Introduction: End Stage Renal Disease (ESRD) is one of the most costly chronic diseases in the industrialized world. In the U.S., more than $27 billion is expended annually for the care of 400,000 dialysis patients. Creation and maintenance of access shunts is one of the principal challenges associated with dialysis, and accounts for 15% of all ESRD-related expenses. A more effective solution to hemodialysis access remains one of the key objectives in vascular surgery today. Previously we reported promising results with the first
human patients to receive a completely autologous tissue engineered vascular graft (TEVG) for hemodialysis access. With time points out to 3 years, we observed a 2.4-fold reduction in events relative to the pre-enrollment rates with the standard of care. The complexities of the autologous model, however, make it difficult to translate to widespread clinical use. We hypothesized that an allogeneic TEVG, available ‘off-the-shelf,’ would have similar benefits and may demonstrate improved efficacy and cost-effectiveness relative to synthetic grafts. Here we report the first human use of an allogeneic TEVG.
TEVGs were built from allogeneic fibroblasts using a process termed Sheet-based Tissue Engineering. 30 cm long grafts with a diameter of 4.8 mm were built from cellular sheets without the inclusion of exogenous biomaterials. The lab-grown grafts were implanted as a shunt between the brachial artery and the axillary vein in three patients with ESRD. No HLA matching was performed. Results: With time points ranging from 1-7 months, all grafts are patent, with flow rates in excess of 600 ml/min. Doppler ultrasound exams show a normal pulse wave, and no changes in diameter or wall structure. Blood laboratory results are all within expected ranges, and lymphocytotoxic cross reactivity tests were uniformly negative. Conclusion: The allogeneic TEVGs do not initiate short-term immune reactions, and appear to tolerate both the hemodynamic loads and the needle punctures associated with hemodialysis access. This short-term result, coupled with the dramatic reduction in event rate for the autologous studies, suggests that an off-the-shelf TEVG with improved efficacy relative to the standard of care may finally be within reach.