Mid-term clinical results of tissue-engineered vascular autografts


Matsumura,-Goki; Shin'oka,-Toshiharu; Hibino,-Narutoshi; Saito,-Satoshi; Sakamoto,-Takahiko; Ichihara,-Yuki; Hobo,-Kyoko; Miyamoto,-Shin'ka; Kurosawa,-Hiromi (Tokyo Women's Medical Univ., School of Medicine, Tokyo (Japan) Prosthetic and bioprosthetic materials currently in use lack growth potential and therefore must be repeatedly replaced in pediatric patients as they grow. Tissue engineering is a new discipline that offers the potential for creating replacement structures from autologous cells and biodegradable polymer scaffolds. In May 2000, we initiated clinical application of tissue-engineered vascular grafts seeded with cultured cells. However, cell culturing is time-consuming, and xenoserum must be used. To overcome these disadvantages, we began to use bone marrow cells, readily available on the day of surgery, as a cell source. Since September 2001, tissue-engineered grafts seeded with autologous bone marrow cells have been implanted in 44 patients. The patients or their parents were fully informed and had given consent to the procedure. A 3 to 10 ml/kg specimen of bone marrow was aspirated with the patient under general anesthesia before the skin incision. The polymer tube serving as a scaffold for the cells was composed of a copolymer of lactide and epsilon-caprolactone (50:50) which degrades by hydrolysis. Polyglycolic or poly-l-lactic acid woven fabric was used for reinforcement. Twenty-six tissue-engineered conduits and 19 tissue-engineered patches were used for the repair of congenital heart defects. The patients' ages ranged from 1 to 24 years (median 7.4 years). All patients underwent a catheterization study, CT scan, or both, for evaluation after the operation. There were 4 late deaths due to heart failure with or without multiple organ failure or brain bleeding in this series; these were unrelated to the tissue-engineered graft function. One patient required percutaneous balloon angioplasty for tubular graft-stenosis and 4 patients for the stenosis of the patch-shaped tissue engineered material. Two patients required re-do operation; one for recurrent pulmonary stenosis and another for a resulting R-L shunt after the lateral tunnel method. Kaplan-Meier analysis in relation to patients' survival was 95% within 3 years. There was only 1 patient (who underwent a total cavo-pulmonary connection procedure) requiring re-intervention in the tubular graft group and the material-related event-free rate was 96% within 3 years. This tissue-engineering approach may provide an important alternative to the use of prosthetic materials in the field of pediatric cardiovascular surgery. As it is living tissue, these vascular structures may have the potential for growth, repair, and remodeling. However, this approach is still in its infancy, further studies to resolve the problems presented, and longer follow-up in patients are necessary to confirm the durability of this approach.