Articles | Volume 4, issue 2
Primate Biol., 4, 153–162, 2017

Special issue: Stem cells in non-human primates

Primate Biol., 4, 153–162, 2017

Research article 18 Aug 2017

Research article | 18 Aug 2017

Overcoming barriers to reprogramming and differentiation in nonhuman primate induced pluripotent stem cells

Jacob J. Hemmi, Anuja Mishra, and Peter J. Hornsby Jacob J. Hemmi et al.
  • Barshop Institute and Department of Physiology, University of Texas Health Science Center San Antonio, San Antonio, TX 78245, USA

Abstract. Induced pluripotent stem cells (iPS cells) generated by cellular reprogramming from nonhuman primates (NHPs) are of great significance for regenerative medicine and for comparative biology. Autologously derived stem cells would theoretically avoid any risk of rejection due to host–donor mismatch and may bypass the need for immune suppression post-transplant. In order for these possibilities to be realized, reprogramming methodologies that were initially developed mainly for human cells must be translated to NHPs. NHP studies have typically used pluripotent cells generated from young animals and thus risk overlooking complications that may arise from generating iPS cells from donors of other ages. When reprogramming is extended to a wide range of NHP species, available donors may be middle- or old-aged. Here we have pursued these questions by generating iPS cells from donors across the life span of the common marmoset (Callithrix jacchus) and then subjecting them to a directed neural differentiation protocol. The differentiation potential of different clonal cell lines was assessed using the quantitative polymerase chain reaction. The results show that cells derived from older donors often showed less neural marker induction. These deficits were rescued by a 24 h pretreatment of the cells with 0.5 % dimethyl sulfoxide. Another NHP that plays a key role in biological research is the chimpanzee (Pan troglodytes). iPS cells generated from the chimpanzee can be of great interest in comparative in vitro studies. We investigated if similar deficits in differentiation potential might arise in chimpanzee iPS cells reprogrammed using various technologies. The results show that, while some deficits were observed in iPS cell clones generated using three different technologies, there was no clear association with the vector used. These deficits in differentiation were also prevented by a 24 h pretreatment with 0.5 % dimethyl sulfoxide.

Short summary
In these studies induced pluripotent stem cells (iPS cells) were generated from donors across the life span of the common marmoset (Callithrix jacchus) and were subjected to a directed neural differentiation protocol. Additionally chimpanzee (Pan troglodytes) iPS cells were generated. Both aged marmoset iPS cells and chimpanzee iPS cells showed defects in their ability to differentiate. However, most of these defects were able to be overcome by a brief treatment with dimethyl sulfoxide.