The Matrix Reprogrammed: a Revolution in the Field of Stem Cells

Since their discovery, pluripotent stem cells have been thought to be the driving force of regenerative medicine. The most well-known source of pluripotent stem cells is the embryo and its embryonic stem cells. However, controversy surrounds their use due to the destruction or manipulation of the embryo. In 2012, Professor Shinya Yamanaka and Sir John Gurdon were awarded the 2012 Nobel Prize for the discovery that mature cells can be reverted back to a pluripotent status. These cells were referred to as induced pluripotent stem cells, or iPSCs, and can be engineered following the introduction of four specific genes (c-MYC, KLF4, OCT3/4, and SOX2) and subsequent selection for FBX15 expression (Takahashi et al., 2006). This breakthrough discovery for generating iPSCs allows one to bypass the need for embryos. In addition, it eliminates the risk of immune rejection after transplantation since individuals can have their own pluripotent stem cell line administered as a therapeutic. Unfortunately, their utilization holds significant risks due to the introduction of viruses to genomically alter the cells and the potential expression of oncogenes. There is, therefore, a need for alternative methods for production of pluripotent cells.

Recently, Dr. Obokata and colleagues from the Harvard Medical School and the RIKEN Center for Developmental Biology reported the discovery of a stimulus-triggered acquisition of pluripotency (STAP) in mouse cells. They noticed that after a short mild-acid treatment, CD45+ cells could be reprogrammed and become pluripotent. The promoters of pluripotent markers, such as OCT4 and Nanog, were shown to be heavily demethylated. Cells also expressed high levels of pluripotent markers, but not early lineage-specific marker genes. Unlike embryonic stem cells, STAP cells were not able to self-renew, form colonies in a dissociation environment or remain stable in culture, but could be easily derived into expandable pluripotent cell lines. Interestingly, similar results were obtained with cells from different tissue origins. Finally, STAP cells generated from CD45+ cells were used in a blastocyst injection assay. All chimeric mice developed normally and CD45+-derived STAP cells were found in all tissues examined. STAP cells were also capable of producing an entire embryonic structure on their own in a tetraploid complementation assay.

This discovery offers great promise in the area of personalized medicine and could have a huge impact on stem cell research in terms of cost and time. Unfortunately, it also raises more questions than answers. Is the genetic information in these STAP cells still of quality? What is the complete methylation status and the histone modification profile of STAP cells? Are the STAP cell lines stable? What is the mechanism behind such a phenomenon? Could it be the release of paracrine signals following the damage from mild-acid treatment or could it be via internal coping mechanisms involving key survival factors such as HSPs, NF-κB or p53? Why are teratoma and teratocarcinoma not often seen in vivo following exposure to an environmental stress? And most importantly, can these results be constantly reproduced not only in mouse cells but also in human cells?

Enzo Life Sciences offers a variety of products to study STAP cells and decipher the mechanisms behind this reprogramming phenomenon including genomic, transcriptomic and epigenetic analysis kits and ELISA kits; some of which are described below:

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