Replacement of Human Anterior Cruciate Ligaments with Pig Ligaments: A Model for Anti-Non-Gal Antibody Response in Long-Term Xenotransplantation

Stone, Kevin R.1; Abdel-Motal, Ussama M.2; Walgenbach, Ann W.1; Turek, Thomas J.1; Galili, Uri2,3

doi: 10.1097/01.tp.0000250598.29377.13
Original Articles: Xenotransplantation

Background. Understanding anti-non-gal antibody response is of significance for success in xenotransplantation. Long-term anti-non-gal response in humans was studied in patients transplanted with porcine patellar tendon (PT) lacking α-gal epitopes, for replacing ruptured anterior cruciate ligament (ACL).

Methods. Porcine PTs were treated with recombinant α-galactosidase to eliminate α-gal epitopes and with glutaraldehyde for moderate cross-linking of collagen fibers. The processed pig PTs were implanted to replace ruptured ACL in patients.

Results. In five of six evaluable subjects, the xenografts have continued to function for over two years and passed all functional stability assessments. Thus, processed porcine PT seems to be appropriate for replacing ruptured human ACL. Enzyme-linked immunosorbent assay and Western blot studies indicated that all subjects produced anti-non-gal antibodies against multiple pig xenoproteins, but not against human ligament proteins. Production of anti-non-gal antibodies peaked two to six months posttransplantation and disappeared after two years.

Conclusions. These antibodies contribute to a low-level inflammatory process that aids in gradual xenograft replacement by infiltrating host fibroblasts that align with the pig collagen “scaffold” and secrete collagen matrix. The assays monitoring anti-non-gal antibodies will help to determine whether long-term survival of live organ xenografts requires complete suppression of this antibody response.

1 The Stone Clinic and CrossCart, San Francisco, CA.

2 Department of Medicine, University of Massachusetts Medical School, Worcester, MA.

This study was supported by CrossCart Inc.

3 Address correspondence to: Uri Galili, Ph.D., Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605.

E-mail: uri.galili@umassmed.edu

Received 18 July 2006. Revision requested 17 August 2006.

Accepted 15 October 2006.

© 2007 Lippincott Williams & Wilkins, Inc.