| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2094442 | Stem Cell Research | 2011 | 13 Pages |
Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed > 70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor.
Research Highlights► Primate embryonic stem cells (nhpESCs) associate with the ICM in mouse chimera. ► nhpESCs do not mingle or proliferate with mouse tissues in outgrowth experiments. ► Mouse-nhpESC chimeric blastocyst produce viable fetuses after embryo transfer. ► nhpESC do not contribution to any mouse chimeric fetus by ICC, PCR and MRI analysis. ► Interspecies primate-mouse chimera may not be a good pluripotency test for nhpESCs.
