Nuclear Transplantation Corrects Immune Deficiency

A mouse model has been used to establish for the first time that a combination of nuclear transplantation, gene therapy, and embryonic stem cell differentiation can be used to create custom-tailored cellular therapies for genetic disorders such as immune deficiency.
The research was conducted at the Whitehead Institute (Cambridge, MA, USA) and was posted on the Cell website on March 8, 2002.

Scientists have been able to use nuclear transfer to create embryonic stem cells and differentiate them in culture to create many different cell types, including muscle, neurons, and hematopoietic stem cells, which are precursors to all immune and blood cells. However, they have never shown that the cells created in culture could be reintroduced into an animal to treat a disease.

In the current study, skin cells from a mouse, which was completely immune deficient, were used to create a cellular therapy that was able to partially restore immune function in the mouse. The nucleus was removed from an egg and replaced with the nucleus from a skin cell of an adult mouse with a genetic immune deficiency. In this procedure, the egg resets the developmental clock of the adult nucleus, and the reprogrammed cell starts developing into an embryo that is genetically identical to the donor cell. "Though the immune system was not completely restored, there was enough improvement to predict that a comparable result in humans would translate into a significant clinical benefit, says George Daley, head of one research team.

"This is a proof-of-principle experiment, which shows that nuclear transplantation therapy may be possible for human application. Furthermore, it shows that gene therapy can be incorporated into the approach to correct genetic mutations in defective cells without affecting the germ line,” added Rudolph Jaenisch, head of the other research team. "While these results show nuclear transplantation therapy can work in principle, there are technical issues that we are working on now.”




Related Links:
Whitehead Institute