title: Replacement of human anterior cruciate ligaments with pig ligaments: a model for anti-non-gal antibody response in long-term xenotransplantation.
abstract: 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 alpha-gal epitopes, for replacing ruptured anterior cruciate ligament (ACL).
  
  
  METHODS
  Porcine PTs were treated with recombinant alpha-galactosidase to eliminate alpha-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.
authors.affiliation: The Stone Clinic and CrossCart, San Francisco, CA, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Stone
authors.forename: Ussama M
authors.initials: UM
authors.lastname: Abdel-Motal
authors.forename: Ann W
authors.initials: AW
authors.lastname: Walgenbach
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Turek
authors.forename: Uri
authors.initials: U
authors.lastname: Galili
mesh_terms: D000328:Adult; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D000917:Antibody Formation / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018448:Models, Immunological; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000939:Epitopes; D000519:alpha-Galactosidase