1919.4 Overcoming Challenges
9.4.1 Somatic Cell Nuclear Transfer
The two major challenges faced with the use of pluripotent human ES cells include
immunorejection by the recipient and the ethical concerns regarding destruction of
human embryos. The best approach to overcome these drawbacks is to reprogramme
a fully differentiated somatic cell to a level of pluripotency suitable for clinical use.
To generate pluripotent ES cells, adult stem cells can be obtained from the patient
by biopsy; the best source of cells in humans is still not known and can be repro-
grammed to form an early embryo (Lovell-Badge 2002 ). This is done by somatic
cell nuclear transfer where the somatic cell nucleus is injected into an unfertilised
enucleated oocyte (see Fig. 9.6 ). Cytoplasmic factors present in mature metaphase
II-arrested oocytes have a unique ability to reprogramme the transplanted somatic
cell nuclei to an embryonic state (Tachibana et al. 2013 ). This would be cultured
in vitro to the blastocyst stage and the cells from the inner mass used to derive ES
cells. Since these techniques use unfertilised eggs, these do not present the same
ethical concerns regarding destruction of human embryos. Making patient-specifi c
cells and transplanting them back in the patient should overcome problems of
immune rejection (Guha et al. 2013 ) as the nuclear genomes of the resulting human
ES cells would be identical to those of the donors of the somatic cells and thus are
purported to be the optimal medical use of human ES therapy (Medicine and
Council 2005 ).
Fig. 9.5 Overview of current optimization possibilities and GMP processing as well as future
developments that need to be made before ES cell can enter clinical trials
9 Human Embryonic Stem Cells and Associated Clinical Concerns