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Presentation
The network and its partners
History of transplantation  |
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NEW FRONTIERS IN TRANSPLANTATION
innovative therapies in transplantation
Organs transplantation has become at the end of the 20 th century, a main therapeutic solution especially regarding the organ shortage, putting in jeopardy patients survival.
Though the technique itself, which consists in placing a vascularized organ in another person, has been developped by the pionneer school of Lyon (Carel, Jaboulay) at the begining of the 20 th century, it is not before 1950 that transplantation meets great success with the successful kidney graft between twins (Boston, Paris), with the discovery of the tissue antigenes (HLA system, Jean Dausset, who received the Nobel Prize in 1980), allowing matchings and above all avoiding non compatibility between donors and recipients. The first liver transplants will then take place (Starzl, 1963), then heart transplants (Barnard, 1967), then other organs such as pancreas, intestines, lungs. The real 'takeoff' in transplantationwill occured in the 80's with the discovery of Ciclosporine A, allowing to reduce tremendously the impact of rejection and as a consequence to increase graft survival.
The current transplantation state, benefiting from all these main progress, represents a important activity
(4664 transplantations in France in 2007), allowing patients to be alive and who would have died a quarter of a century ago. Main current stakes for transplantation are included in our aims #1, #2 and #3, but also in the development of new frontiers such as composite tissue allografts, xenografts and new therapies against rejection consequences.
composite tissue allografts
Composite tissue allograft (CTA) was first performed for the hand (in 1998) in Lyon by Pr. Dubernard followed by face allograft (in 2005, in collaboration with Pr. Duvauchelle, Amiens). These grafts are called composite tissue allografts for they include skin, muscles, bones, vessels and nerves which can induce rejection feedback. This strategy is highly innovative for various extends:
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CTA proposes a new method in treatment for the most severe functional and motor handicaps, and not only make up for organ failure.
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CTA generates an immune response which is especially interesting in terms of study, from the recipient point of view (in particular by developping new animal models for composite grafts),
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The re-innervation of new parts of the body makes us wonder about comprehension of neurological mechanisms concerning body representation and process of the sensory cortex level recovery.
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Face allograft strategy must be enlarged to other patients and in the future, this strategy might find an interest in limited segments of the face, that could not be repaired otherwise.
xenotransplantation
Use of pig's organs in human might be an alternate solution to the well-known organ shortage. However, differences between pig and human generate quite important and fast responses, and consequently lead to limited survival in primates untill now. The possiblity to modify genetically few categories of pigs with introducing human genes (gene transfer), genes able to limit anti-pig response, and the disappearance (Knock out by nuclear transfer) as well of the main target response in pigs (Gal). This response generated by human antibodies have allowed longer lasting survivals of pig organs in primates. The team of Nantes has already a good experience for it was the first to use pigs called DAF for kidney grafts in baboons. This team is studying:
1) regulatory mechanisms occuring during pig endothelial cell activation when compared to immune cells in human and the way to protect them.
2) experimental models for kidney and neurons xenotransplantation between transgenic pigs (various transgenic and Gal KO pigs) and between baboons in order to study and thus block responses against these new animals.
new immusuppressive headways
A better understanding which is becoming gradually more precise for reactions againts a graft, allows us to think about new inhibitions paths of these responses. Thus, one of the molecule essential to the activation message of a donor's lymphocyte, leading to rejection, the CD28 molecule, can be blocked by an innovative reagent developped by Dr. Vanhove (Nantes), sc28AT. Experiments on primates are currently being carried out to test animal tolerance to this molecule and its efficiency to prevent kidney graft rejection, before being proposed for clinical trial in human.
