A major breakthrough for enabling generating pluripotent stem cells that can give rise to every cell type in the body, has been the direct in vitro reprogramming of somatic cells to pluripotency, a method by which adult cells are genetically reprogrammed to an embryonic stem cell (ESC)–like state. These reprogrammed cells are called induced Pluripotent Stem Cells (iPSCs) and they currently constitute an essential model for understanding normal and pathological embryonic development. However, unlike for mouse iPSCs/ESCs, existing protocols for culturing human iPSCs/ESCs (termed conventional or primed), are very inefficient unless they have undergone extensive optimisation, which is mostly based on empirical observations and therefore, highly cumbersome. Importantly, the low efficiency and pre-existing lineage biases during differentiation (referred to as priming) of human PSCs (iPSCs or ESCs), translates to a very poor yield and limited functionality. Notably, this deficiency is even more significant in human iPSCs produced by reprogramming somatic cells with exogenous factors as in this process the iPSCs have a tendency to retain somatic cell epigenetic memory. The latter is particularly important because human iPSCs are patient-specific and devoid of ethical concerns, thus are usually preferred over embryo derived human ESCs.
Over the last 3 years and with the help of this ERC-PoC grant my lab made an important stem cell growth condition platform that may transform the enormous potential of stem cell science into viable and sustainable treatments for degenerative and age-related diseases. In particular, we were the first group worldwide who successfully managed to generate Extracellular-signal-Regulated Kinases (ERK) signalling independent human naïve PSCs (both ESCs and iPSCs) that are more equivalent to those derived from mice and known to be extremely flexible and robust. These Human naïve PSCs constitute a completely new category of human stem cells that is characterised by an earlier developmental stage, i.e. they are more “primitive” than typical human PSCs and equivalent to mouse iPSCs. We managed to do so by employing a panel of different inhibitors and cytokines to produce a novel Naïve Human Stem cell Medium (NHSM) that allows the acquisition of many naïve features that were previously observed only in mice. Importantly, this new pluripotent configuration, not only comes in different molecular flavours, but also appears to have different and enhanced functional properties. For instance, we were the first to be able to successfully reconstitute in vitro the early human cells that give rise to either oocytes or spermatozoa, known as Primordial Germ Cells (PGCs). Importantly, NHSM based discoveries have been commercialised within a multiple products and sold by the top leading stem cell product company worldwide.
