Why “Successful” Mouse “Therapeutic” Cloning Really Didn’t Work
So-called “therapeutic” cloning is proposed for producing genetically matched tissues for transplant by creating a cloned embryo of the patient to be treated, and then harvesting the embryonic stem cells from the cloned embryo. In theory the patient would not reject the cells from the cloned embryo, because the embryo is the patient’s identical twin.
In the first published experiments to test this theory1, researchers started with a mouse that had a genetic defect—an immune deficiency where they lack mature white blood cells called B cells and T cells. A cell was taken from a somatic (body) cell of the mouse (from the tail tip), and the nuclear material of the cell was injected into a mouse egg which had had its nuclear material removed (somatic cell nuclear transplant, a.k.a. cloning.) The cloned embryo was grown in culture to a stage from which embryonic stem cells could be harvested (destroying the embryo.)
Because the mouse had a genetic defect, the embryonic stem cells still contained this defect (being from a clone of the original mouse). Gene therapy was used to “repair” the genetic defect in the cells in culture. The cultured cells were then stimulated to transform into blood cells, and these were transplanted back into the original mouse (the patient) (#1 on the figure).
The hope was that this cycle (mouse to cloned embryo to embryonic stem cells to transplant back into the mouse) would “cure” the mouse of its defect and repair its tissues. However, the experiment failed; the mouse rejected the transplanted cells. The scientists reasoned that this was because there are other immune cells, termed “NK cells”, which were still present in the mouse and which attacked and destroyed the transplant. So in a second attempt (#2 in the figure), the mouse was first treated with antibodies to destroy the NK cells, then the transplant was attempted. Again, the transplant failed, possibly because the NK cells had not all been removed and still attacked and destroyed the transplanted embryonic stem cells.
In a third attempt (#3 in the figure), the scientists transplanted the embryonic cells not into the original mouse, but rather into a different mouse, one which had an additional genetic defect, causing it to lack both B and T cells as in the original mouse, as well as lacking any NK cells which might attack the transplant. However, this resulted in less than 10% success in treating the genetic disease in the mouse and restoring its B and T cells.
In a fourth experiment (#4 in the figure), the genetically “repaired” embryonic stem cells were used to create new cloned embryos, and these embryos were implanted in a surrogate mother and brought to birth. From these born, genetically “repaired” mice, bone marrow or blood was harvested and used to transplant back into the original, genetically defective mouse. The transplants of these “adult” stem cells successfully corrected the genetic problem of the original mouse (the patient.)
What does it all mean? “Therapeutic” cloning is supposed to produce matched embryonic stem cells that can be transplanted back into the original patient and not be rejected. Yet the original “patient” in these experiments still rejected the supposedly matched cells from its cloned embryo. Even transplantation into a different “patient” who should not have rejected the cells was still largely unsuccessful. The scientists in their paper note: “Our results raise the provocative possibility that even genetically matched cells derived by therapeutic cloning may still face barriers to effective transplantation for some disorders.” In other words, therapeutic cloning may not always produce matched tissues. In contrast, “adult” stem cells from the born cloned mice were successful in matching the original patient and correcting the problem. This indicates that the only successful therapy using cloned embryos would be through “reproductive” cloning, to produce born clones who can serve as tissue donors for patients.
- Reference:
1. W.M. Rideout et al., “Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy,” Cell Immediate Early Publication, published online March 8, 2002; DOI:10.1016/S0092867402006815 ↩