Non-human primates, owing to their genetic, physiological, and behavioral similarities to humans, are increasingly vital in stem cell therapy research as well as in preclinical trials. However, ethical concerns and costs have prompted a search for alternative approaches. Recently, scientists from Kunming University of Science and Technology introduced a xeno-free culture system for cultivating monkey pluripotent stem cells (PSCs). These cells exhibit unique gene expression and genome-wide hypomethylation patterns.
These xeno-free PSCs can be derived from blastocysts, converted from established PSC lines, or generated by somatic cell reprogramming. It was shown that expression of signaling pathways components may increase the potential for chimera formation. Crucially for biomedical applications, it was also able to integrate bioluminescent reporter genes into monkey PSCs and track them in chimeric embryos in vivo and in vitro.
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The engineered cells retained embryonic and extra-embryonic developmental potential, capable of differentiating into all three germ layers as well as into reproductive germ-like cells, both in vitro and in vivo. Meanwhile, by integrating AkaLuc, a bioengineered luciferase gene, into the genome of monkey stem cells, a chimeric monkey carrying bioluminescent cells, which were able to track chimeric cells for more than 2 years in living animals, was successfully created. Thus, it is allowed to track the proliferation and migration of chimeric cells within the monkey in vivo.
This advancement, described in a Protein & Cell paper, paves the way for primate organoid research and xenotransplantation, offering a powerful tool for future clinical studies. Furthermore, the chimerism test not only confirms stem cell pluripotency but also explores the potential of organ compensation in NHPs, holding broad implications for primate stem cell engineering and clinical applications.