Ask Usain Bolt, Yelena Isinbayeva, or Lindsey Vonn and they will tell you that Gold is the only thing that matters. To them, it came in the guise of an Olympic medal (or two), but human pluripotent stem cells (hPSCs) have been in the hunt for a slightly different type of gold to prove their worth.
The ability to form embryonic chimeras and contribute to the developing organism after mouse blastocyst injection represents the “gold” standard as the most stringent test for the in vivo pluripotency, and, therefore, utility, of stem cells. Mouse (m)PSCs have previously passed this test with flying colors, although human (h)PSCs have not, and so some questions on hPSC utility and safety still buzz around many scientists’ ears.
Victoria L. Mascetti and Roger A. Pedersen thought that the inability of hPSCs to efficiently form chimeras might be due to a developmental mismatch – mPSCs resemble the cells of the ICM, known as the “naïve” state, whereas hPSCs resemble a more restricted epithelial stem cell state, known as the “primed” state. So if mPSCs can integrate into the blastocyst-stage embryo where the ICM exists, can hPSCs integrate into a more developed embryo and win gold in the pluripotency stakes?
In their new paper, published in Cell Stem Cell, the authors found that:
- Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) could efficiently form chimeras when injected into stage-matched gastrulating mouse embryos and NOT when injected into the earlier blastocyst-stage embryos.
- Cell tracking found that injected hPSCs, mimicking the embryo’s own cells, migrated and differentiated into cells representative of the three germ layers (endoderm, mesoderm, and ectoderm) so functionally validating the in vivo pluripotency of hPSCs.
- Importantly, injected cells did not form tumors (teratomas) during the time studied.
AND THEY TAKE THE GOLD! This stage-matching strategy now suggests that hPSCs are fully pluripotent, safe, can incorporate and develop normally in the developing embryo, and so are likely to be an important resource for regenerative/reparative therapies. But perhaps the most important aspect of this study is that the ability of hPSCs to form chimeras may help us to study the early stages of human development in an ethically acceptable way.
They didn’t do it quickly, but they did manage it with a bit of style. See how hPSCs eventually won their gold at Cell Stem Cell, December 2015.