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Previous Volume 357:1451-1453 October 4, 2007 Number 14 Next

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To the Editor: A material that will approach the efficacy of native vein has been widely sought.¹ Using autologous cells and a technique termed sheet-based tissue engineering, we were able to produce autologous tissue-engineered blood vessels with physiologic mechanical properties.² No synthetic or exogenous materials were used; instead, the vessels were created with the use of autologous fibroblasts and endothelial cells harvested from a small biopsy specimen of skin and superficial vein. Here we report on the preliminary use of these tissue-engineered blood vessels in an adult arterial model.

Ten patients receiving hemodialysis whose arteriovenous shunts were failing were enrolled in this study. The subjects had typical risk factors for end-stage renal disease, including previously failed dialysis-access grafts, diabetes, controlled hypertension, and obesity. Patients ranged in age from 29 to 89 years (mean [±SD], 68±17). Vessel patency was evaluated by means of Doppler and angiographic imaging. Mechanically viable vessels were created with autologous cells for each patient. The average burst pressure among 54 vessels was 3340±849 mm Hg, which compares favorably with native veins.³

The primary objective of this study was to demonstrate that a tissue-engineered blood vessel produced in vitro could withstand the challenges of arterial pressure produced by an arteriovenous fistula for at least 3 months. After this observation period, grafts were punctured for hemodialysis access. To date, the first six patients have had vessels implanted and have been followed for up to 13 months.

The tissue-engineered blood vessel in Patient 1 (Figure 1) was used for more than 13 months, until the patient underwent successful kidney transplantation. At 11.5 months, an aneurysm was noted near an area that had many punctures. A small portion of the vessel wall was resected, and the tissue-engineered blood vessel continued to function until the kidney transplantation. In total, the 14-cm-long graft was punctured more than 200 times.

View larger version (46K): [in this window] [in a new window]   Figure 1. The Tissue-Engineered Blood Vessel Preoperatively (Panel A), at 3 Months after Implantation (Panel B, Computed Tomographic Angiography), and at 12 Months after Implantation (Panel C, Doppler Ultrasonography). VA denotes venous anastomosis, and AA arterial anastomosis.

 
Patient 2 died at day 39 of unrelated causes with a functioning tissue-engineered blood vessel. The vessel in Patient 3 had a thrombogenic failure at 12 weeks, attributed to a low postoperative flow rate (<500 ml per minute) and a moderate, diffuse dilatation that further reduced flow velocity. At up to 5 months after implantation, Patients 4, 5, and 6 have functioning grafts without complications.

Compliance measurements derived by ultrasonography at 5 months show a 4.8-fold increase for Patient 1 (3.1 to 15.0% per 100 mm Hg) and a 2.7-fold increase for Patient 4 (2.3 to 6.2% per 100 mm Hg) in compliance relative to preoperative values, without concomitant dilatation or evidence of mechanical degradation. This may indicate the formation of an elastic component, which would be consistent with our preclinical results.

Although these are clearly early results, we have demonstrated in 24 patient-months of use that this new approach may be feasible. This transition to human use represents an important milestone for cardiovascular engineering.⁴

Nicolas L'Heureux, Ph.D.
Todd N. McAllister, Ph.D.
Cytograft Tissue Engineering
Novato, CA 94949
nico{at}cytograft.com

Luis M. de la Fuente, M.D.
Instituto Argentina de Diagnostico y Tratamiento
1122 Buenos Aires, Argentina

Drs. L'Heureux and McAllister report holding stock in Cytograft Tissue Engineering.

References

1. Conte MS. The ideal small arterial substitute: a search for the Holy Grail? FASEB J 1998;12:43-45. [Free Full Text]
2. L'Heureux N, Dusserre N, Konig G, et al. Human tissue-engineered blood vessels for adult arterial revascularization. Nat Med 2006;12:361-365. [CrossRef][ISI][Medline]
3. Schaner PJ, Martin ND, Tulenko TN, et al. Decellularized vein as a potential scaffold for vascular tissue engineering. J Vasc Surg 2004;40:146-153. [CrossRef][ISI][Medline]
4. Weinberg CB, Bell E. A blood vessel model constructed from collagen and cultured vascular cells. Science 1986;231:397-400. [Free Full Text]

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