Is rejection of human transplanted animal tissues avoidable?

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The demand for organ and tissue transplantation (heart, kidney, cardiac valves, cartilage) already far surpasses the number of available donors. The lack of resources has led biomedical researchers to explore the use of animal donors as an attractive and unlimited source for biological devices (xenotransplantation). Xenogeneic tissues, the tissue that are harvested from common animals such as pigs, sheep, cows, horses, are currently employed in clinical practice to create biological prostheses for the substitution of specific structures like heart valves, ligaments, pericardium etc.. and in the repair of various damaged body costituents (gastric-mucosa, nerves, cartilage). It is well know by many scientific studies that xenogeneic tissues express superficial molecules, called epitopes, alpha-Gal in primis, but also the major histocompatibility complex (MHC), capable of triggering hyperacute and acute vascular rejection phenomena. An epitope is definied as an antigenic determinant, something that it is not recognized as a “personal effect” by the immune system cells (B cells, T cells) and antibodies of the recipient organism. Once a tissue is recognised as non-self, a series of events are triggered ending in vascular thrombosis.

Currently, commercially available xenogeneic bioprosthes are processed with treatments which have not been proven able to completely mask or inactivate such epitopes. Most common methods involves the use of chemicals to stabilize matrices (the main component of tissues); these agents penetrate deep into the substrate and cover it quite permanently like a molasses. Glutaraldehyde fixative is one of them and even if it allows the clinical use of tissues, it is toxic for cells sorrounding the site of implantation and for the graft itself, therefore prostheses biological integration is not possible.

The ability to ascertain alpha-Gal and MHC epitopes removal from a xenogeneic tissue is closely related to the possibility of its quantitative determination. Recently, a new patented test has been processed by prof. Gino Gerosa’s research team at the Cardiac Surgery Reserch Lab of the University of Padova. The test developed assesses the presence of still unmasked alpha-Gal epitopes that rather than triggering a hyperacute rejection, due to reduction in number, lead to a chronic phlogosis that have dramatic effects in the mid-long term after the bioprostheses has been implanted, especially when this xenogeneic tissue is used to construct heart valves substitutes.

Analysis of currently commercial heart valve bioprosthes assessed, for the first time, the presence of the alpha-Gal
epitope used for about 40 yrs for surgical reasons. Such quantification might provide indications of biocompatibility relevant for the selection of bioprosthetic devices and an increase in the confidence of the patient. It might
become a major quality control tool in the production and redirection of future investigation in the quest for alphaGal-free long-lasting substitutes.

These are the first scientific results that shed light on one of the most critical cause for mid-long term failure of heart valve bioprosthese.

Related article:

First quantification of alpha-Gal epitope in current glutaraldehyde-fixed heart valve bioprostheses by Naso F e al. Xenotransplantation. 2013 doi: 10.1111/xen.12044

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