Unit Three. The Continuity of Life
13. The New Biology
13.8. Therapeutic Use of Cloning
While exciting, the therapeutic uses of stem cells to cure leukemia, type I diabetes, Parkinson’s disease, damaged heart muscle, and injured nerve tissue were all achieved in experiments carried out using strains of mice without functioning immune systems. Why is this important? Because had these mice possessed fully functional immune systems, they almost certainly would have rejected the implanted stem cells as foreign. Humans with normal immune systems might well refuse to accept transplanted stem cells simply because they are from another individual. For such stem cell therapy to work in humans, this problem needs to be addressed and solved.
Cloning to Achieve Immune Acceptance
Early in 2001, a research team at the Rockefeller University reported a way around this potentially serious problem. Their solution? They first isolated skin cells from a mouse, then using the same procedure that created Dolly, they created a 120-cell embryo from them. The embryo was then destroyed, its embryonic stem cells harvested and cultured (figure 13.19) for transfer to replace injured tissue. This procedure is called therapeutic cloning. Therapeutic cloning and the procedure that was used to create Dolly, called reproductive cloning, are contrasted in figure 13.20. You can see that steps 1 through 5 are essentially the same for both procedures, but the two methods proceed differently after that. In reproductive cloning, the blastocyst from step 5 is implanted in a surrogate mother in step 6a, developing into a baby that is genetically identical to the nucleus donor, step 7a. In therapeutic cloning, by contrast, stem cells from the blastocyst of step 5 are removed and grown in culture, step 6. These stem cells are developed into particular tissue types, such as pancreatic islet cells in step 7, and can then be injected or transplanted into a patient that needs them, such as a diabetic patient, where the new islet cells can begin producing insulin.
Figure 13.19. Embryonic stem cells growing in cell culture.
Embryonic stem cells derived from early human embryos will grow indefinitely in tissue culture. When transplanted, they can sometimes be induced to form new cells of the adult tissue into which they have been placed. This suggests exciting therapeutic uses.
Therapeutic cloning, or, more technically, somatic cell nuclear transfer, successfully addresses the key problem that must be solved before embryonic stem cells can be used to repair damaged human tissues, which is immune acceptance. Because stem cells are cloned from the body’s own tissues in therapeutic cloning, they pass the immune system’s “self” identity check, and the body readily accepts them.
Gene Reprogramming to Achieve Immune Acceptance
In therapeutic cloning, the cloned embryo is destroyed to obtain embryonic stem cells. What is the moral standing of a six- day human embryo? Considering it a living individual, many people regard therapeutic cloning to be ethically unacceptable. Recent research discussed on the previous page suggests an alternative approach that avoids this problem: reprogramming adult cells into embryonic stem cells by introducing just a few genes into the adult cells. The genes are so-called transcription factors, turning on key genes that act to reverse the “shut off” epigenetic changes that have occurred during development of the adult cells. Human applications, if even possible, are probably far into the future, but the possibility of reprogramming adult cells is exciting.
Figure 13.20. How embryonic stem cells might be used for therapeutic cloning.
Therapeutic cloning differs from reproductive cloning in that after the initial similar stages, embryonic stem cells from the early embryo are extracted, grown in culture, and added to a tissue of the individual who provided the nucleus. By contrast, in reproductive cloning (forbidden in humans), the embryo would be preserved to be implanted and grown to term in a surrogate mother. It is this latter procedure that was done in cloning Dolly the sheep.
Key Learning Outcome 13.8. Therapeutic cloning involves initiating blastocyst development from a patient's tissue using nuclear transplant procedures, then using the blastocyst's embryonic stem cells to replace the patient's damaged or lost tissue. Gene reprogramming of adult tissue cells may allow a less controversial approach.