Cellules souches embryonnaires et clonage thérapeutique

Embryonic stem cells and therapeutic cloning

Unité de biologie du développement et biotechnologie, Inra, 78352 Jouy en Josas, France

^* renard@jouy.inra.fr

Résumé

Le clonage permet de reconstituer un embryon qui, une fois transplanté dans une femelle receveuse, pourra se développer à terme. L’importance de la question éthique soulevée par la perspective d’application de cette technique à l’homme a rapidement conduit à distinguer le clonage reproductif aboutissant à la naissance d’un jeune, du clonage non reproductif dit « clonage thérapeutique » se limitant à la production de cellules embryonnaires. Le recours au clonage reproductif humain fait maintenant l’objet d’une désapprobation quasi unanime dans le monde. Une nouvelle phase commence désormais pour essayer de comprendre la nature des mécanismes moléculaires et cellulaires mis en œuvre. Vu leur complexité, un long chemin reste à parcourir avant que le clonage thérapeutique puisse éventuellement devenir une réalité.

Abstract

The transfer of a somatic nucleus into an enucleated recipient cytoplasm, or cloning, is now used in several mammalian species to generate live and fertile animals. Although of a low efficiency, this technique can be considered as a new mean of reproducing mammals. An alternative use of cloning is to produce embryos at the blastocyst stage from which pluripotent embryonic stem cells will be generated and differentiated in vitro into various tissues with the same immunological status as the nuclear donor organism. This second approach often referred to as therapeutical cloning is today a matter of intense debate on its potential application to human. Recent results in the mouse clearly show that pluripotent cell lines can relatively easily be established from cloned blastocysts and subsequently differentiate in vitro into apparently fully functional tissues. When such embryos are transfered in vivo into foster mothers they however develop poorly to term and result only occasionally in normal offspring. The reasons for these paradoxical results need to be enlightened before deciding on the use of nuclear transfer in human to generate replacement tissues. This will require a better understanding on how the nuclear and cytoplasmic events that occur during the remodelling of a somatic chromatin into an embryonic one can lead to long lasting detrimental effects during fetal and postnatal development.