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.
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: Natasha Anoka; John Nyland; Mark McGinnis; Dave Lee; Mahmut Nedim Doral; David N M Caborn Journal: Knee Surg Sports Traumatol Arthrosc Date: 2011-08-10 Impact factor: 4.342
Authors: Whayoung Lee; Hidetaka Hara; Mohamed B Ezzelarab; Hayato Iwase; Rita Bottino; Cassandra Long; Jagdeece Ramsoondar; David Ayares; David K C Cooper Journal: Xenotransplantation Date: 2016-03-14 Impact factor: 3.907
Authors: Mark R Albertini; Erik A Ranheim; Cindy L Zuleger; Paul M Sondel; Jacquelyn A Hank; Alan Bridges; Michael A Newton; Thomas McFarland; Jennifer Collins; Erin Clements; Mary Beth Henry; Heather B Neuman; Sharon Weber; Giles Whalen; Uri Galili Journal: Cancer Immunol Immunother Date: 2016-05-20 Impact factor: 6.968
Authors: Whayoung Lee; Yuko Miyagawa; Cassandra Long; Burcin Ekser; Eric Walters; Jagdeece Ramsoondar; David Ayares; A Joseph Tector; David K C Cooper; Hidetaka Hara Journal: Cornea Date: 2016-01 Impact factor: 2.651