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

Abstract

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.

The past, present and future in scaffold-based tendon treatments

“…For these reasons, the use of xenografts took off, with numerous products currently available [307,308]. Although positive functional scores and improved movement as early as 6 months post-operation have been reported [309], many studies have demonstrated high failure rates and tearing incidents [310][311][312][313], which may be attributed to processing conditions (e.g. decellularisation, cross-linking, sterilisation) employed to battle immune rejection, which remains the major obstacle for both allogeneic [314,315] and xenogeneic [316] approaches.…”

Anti-Gal and Anti-Non Gal Antibody Barriers in Xenotransplantation

“…Anti-non gal IgG Ab activity in the pig ligament recipients increased on average by 5-10 folds in comparison with pre-implantation serum in each of the patients (Stone et al, 2007). This increase is much lower than the ~100 fold increase in anti-Gal Ab activity observed in the patient receiving intraperitoneal infusion of mouse fibroblasts.…”

“…For such analysis, anti-Gal Abs have to be removed from the tested human sera prior to the assay. This anti-Gal depletion is feasible by adsorption of anti-Gal Ab on rabbit RBC or on glutaraldehyde rabbit RBC (Galili et al, 2001;Stone et al, 2007) since these RBC present the highest number of -gal epitopes among mammalian RBC (Ogawa & Galili, 2006). As described below, studies on anti-non gal Abs in xenograft recipients have indicated that their production is very different from that of elicited anti-Gal Abs.…”

“…The induced antinon gal Ab response peaked 2 -6 months post implantation (Fig. 2) (Stone et al 2007). This Ab response was detectable also after 1 year, but it returned to the pre-implantation level after 2 years.…”

“…A phase I clinical trial on replacement of torn anterior cruciate ligament (ACL) with pig patellar tendon provided a unique opportunity for monitoring anti-non gal Ab response in the absence of immunosuppression in humans, for a period of 2 years (Stone et al 2007). The implanted ligaments and the two attached bone blocks were treated with recombinant -galactosidase in order to eliminate -gal epitopes.…”