INTERSPECIES STRIFE DEFINITION FULL

(2002) demonstrated that the transplantation of hESCs into somite stage chick embryos resulted in the autonomous formation of neural tube-like structure by hESC-derived cells. The pluripotent nature of human embryonic stem cells (hESCs) has been demonstrated in vitro and by teratoma formation in vivo ( Thomson et al., 1998). Human PSC-animal chimeras and the importance of developmental timing We further discuss some important considerations for performing chimeric assays, such as the evolutionary distance between species, the nature of the cells themselves and some of the ethical concerns that have arisen in the field. In this Spotlight article, we provide some examples of how interspecies chimeric assays can and should be applied to determine the developmental potency of human PSCs, somatic stem cells, or cells derived in vitro from stem cells. In addition, it is becoming increasingly important to verify the in vivo functionality of cells derived in vitro from PSCs, or indeed other stem cell types. This is particularly true for human naïve-like PSC lines ( Theunissen et al., 2016), since there are a variety of conditions under which they can be established ( Li et al., 2009 Hanna et al., 2010 Gafni et al., 2013 Takashima et al., 2014 Theunissen et al., 2014). Therefore, in order to uncover the actual potency of human stem cells in vivo, an interspecies chimeric assay becomes crucial. In vitro culture of mouse embryos injected with human PSCs might demonstrate whether these cells have ability to contribute to mouse epiblast ( Masaki et al., 2015) however, further analysis of their differentiation potential is impossible in such a short period of time. For example, ISSCR guidelines (as of 2016) allow for the development of human embryos injected with human PSCs only in vitro and only up to gastrulation. Guidelines from the International Society for Stem Cell Research (ISSCR) and the relevant regulatory authorities of many countries indicate that there are ethical concerns regarding chimeric experiments performed using human or non-human primate embryos, even before the pre-implantation stage. As such, it is best to employ a chimeric assay between the same or closely related species.

INTERSPECIES STRIFE DEFINITION FULL

Given these differences, it is important to remember that a failure to generate full interspecies chimeras using human PSCs does not necessarily mean that the cells are not pluripotent, but possibly that a suitable host species and environment have not yet been identified. These include the structure of ligands and/or adhesive molecules, the developmental system itself, cell proliferation rate and so on. It is worth noting, however, that unlike chimera formation between syngeneic or allogeneic species, there are a number of factors that can differ significantly between species in the xenogeneic setting. For these cells, given the ethical concerns, a xenogeneic setting – meaning cross-species chimerism – is the only possible choice for using a chimeric assay. However, when it comes to human PSCs (), chimeric assays become extremely difficult. This is a convenient and feasible method if one wants to determine the differentiation potential of stem cells derived from laboratory animals such as mice. The ability to contribute to chimera formation across multiple lineages when injected into the pre-implantation blastocyst is still a gold standard for ʻtrue' PSCs, at least when both donor and host cells belong to the same species. However, a definitive conclusion cannot be made until their developmental potency is confirmed in vivo by making a chimera. Whatever pluripotent stem cells (PSCs) we isolate or generate, we usually predict their differentiation potential by gene expression profile or by in vitro functional assays. Although there are other approaches to assess cellular dynamics, such as genetic lineage tracing, the importance of chimeric assays has increased recently alongside advances in the field of stem cell biology.

The generation of chimeras has been a classic and common approach in developmental biology and is used to analyze developmental potency by transplanting cells into a genetically different host.

Interspecies strife definition