Scientists have discovered ways to recreate naive pluripotency (derived from the inner cell mass of a developing embryo) in vitro using either embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) in recent decades. Whereas rodents have shown such naive pluripotency, other species, including nonhuman primates (NHPs), have shown poor chimerism due to the donor cells’ inability to match the developmental state of the host embryos. While some studies have attempted to create chimeric monkeys using PSCs, the fetus was frequently aborted or had low donor cell contributions. Manipulation of cell culture conditions is one proposed solution to this problem.
The components of a cell culture are critical for the viability of the culture. Scientists can influence cell development by varying the concentrations of various ingredients such as substrates and growth factors. The study by Liu and colleagues aimed to test the effects of various human PSC mediums on the establishment of monkey naive embryonic stem cells and to refine the technique for culturing chimeric embryos. One of the media tested was known as 4CL, and it had shown promising results in a 2022 study in Cell using human stem cells. The work of Liu and colleagues made use of cynomolgus monkeys, a common NHP used in laboratory experiments. They created nine stem cell lines by extracting cells from a 7-day-old embryo and cultured them in various mediums.
A selection of the cultured stem cells was injected into monkey embryos aged 4–5 days old and implanted into female monkeys. Twelve of the monkeys became pregnant, and six of them gave birth to live babies. The researchers were able to determine which of the offspring possessed cells that had grown from the stem cells by labeling the injected cells with green fluorescent protein (GFP). One aborted male and one live-birth male possessed such cells and were therefore chimeric. The researchers believe that their findings will aid in the development of novel NHPs for use in biomedical research. NHPs are especially important in the study of neurological disorders and neurodegenerative diseases, where rodent models are limited.
Reference: Cao J, Li W, Li J, et al. Live birth of chimeric monkey with high contribution from embryonic stem cells. Cell. 2023. doi: 10.1016/j.cell.2023.10.005