Primate and human somatic cell nuclear transfer

Introduction Non-human primates (NHPs) are an ideal model in preclinical research due to their remarkable genetic, physiological, and reproductive similarities to humans. NHPs are also critical in areas where basic discoveries in rodent or other animals were difficult to translate to clinical settings. Particularly, reprogramming of somatic cells to pluripotency by somatic cell nuclear transfer (SCNT) is a routine and efficient process in the mouse. However, these protocols were not applicable for human oocytes and embryos [1]. Reproductive cloning by SCNT would also be critical for replication of valuable genotypes or generation of genetically modified NHPs. In this chapter, we summarize the current state of SCNT in NHPs and the efforts to produce human pluripotent stem cells by SCNT-based reprogramming. Nuclear transfer was originally proposed by Spemann (1938) as a method to “recycle” the nuclear genome from embryonic or somatic cells and evaluate its ability to support full-term development [2] (see also Chapters 1 and 22). The concept was first successfully tested by Briggs and King (1952) in amphibia by transplanting nuclei of embryonic blastomeres into enucleated eggs [3]. Later, Gurdon (1962) tested more advanced tadpole intestinal cells and produced viable Xenopus offspring [4]. Due to technical and biological limitations in manipulating oocytes, nuclear transfer experimentations in mammals were not reported until the early 1980s. Initial studies also used nuclei of blastomeres from cleaving preimplantation embryos and these studies demonstrated that enucleated zygotes have only limited utility as recipient cytoplasts [5, 6]. However, unfertilized, mature metaphase II (MII) oocytes provided better reprogramming capacity compatible with full-term development [5, 7]. The first offspring generated by SCNT using an adult somatic cell was Dolly the sheep [8]. Following similar SCNT techniques, researchers have now succeeded in producing live offspring or embryonic stem cells (ESCs) in a number of different mammals (Table 23.1).