Despite the fact that the person would be glowing, we would still recognize the cohesive whole as human. Of course, this should not be our only method of determining what is human. As stated before, though based in science, this method is purely heuristic, and is therefore prone to failure. For instance, scientists may be able to give chimpanzees human facial features in addition to human posture. This would make it easy for a person to mistake the chimp for a human, especially from afar.
International stem cell environments: a world of difference | Nature Reports Stem Cells
What makes this chimpanzee not human, then? Though transgenic transplants can change appearances and characteristics, the one thing it cannot change, as far as evidence shows, is the personality of an entity. Here is where chimeras serve to define what is human. Instead of destroying the human identity by crossing the species barrier, it solidifies the human identity by what it is incapable of changing.
Chimera research is capable of giving mice human immune systems and diseases; it is capable of producing human appendages on a nonhuman embryo; it is even capable of creating interspecies-compatible tissues and organs.
Is This Cell a Human Being? Exploring the Status of Embryos, Stem Cells and Human-Animal Hybrids
However, chimerization is not capable of changing the behavior or personality of an entity. In Suarez et al.
Nicole E. Is This Cell a Human Being? Berlin: Springer-Verlag, Herzfeld, Noreen L. Genetics, Stem Cells, and Cloning.
In many cases, there are significant limitations in the data available to classify the developmental capabilities of cell types, particularly for human cells. Moreover, not all studies agree on the potency of the same cell type. Consequently, as is the case for all classifications, those suggested in Table 2 can only be taken as provisional, and must be interpreted relative to a specific body of work.
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Yet individual studies can be evaluated based on the evidence they present. For example, a recent study of embryonic stem cells ESCs [ 10 ] suggests neither human nor mouse cells produce trophectoderm TE derivatives, a finding that would classify both cell types as pluripotent. In contrast, other studies indicate that human ESCs hESCs are able to produce both trophoblast and syncytiotrophoblast, a finding that would classify hESCs as plenipotent [ 11 , 12 ].
Similarly, several recent studies indicate that subpopulations of mouse ESCs mESCs are able to differentiate as TE derivatives [ 4 , 13 , 14 ], which would classify this subset as plenipotent. In contrast, other studies of mESCs either indicate that TE derivatives can only be induced by artificial manipulation of specific genes [ 15 ] or, conversely, that the great majority of mESCs are able to produce TE derivatives under specific culture conditions [ 16 , 17 ], further illustrating that the potency of specific types of stem cells has not been conclusively resolved in the literature.
Nonetheless, relating the degrees of potency observed in cell lines to the progressive restrictions in potency observed in development Fig. These misapplications fall into four general classes: 1 equating participation in development with the ability to independently generate a developmental sequence, 2 equating the ability of groups of cells to collectively generate a developmental sequence with totipotency of individual cells, 3 equating the expression of early embryonic markers with totipotency, and 4 taking a partial or superficial resemblance to an embryo as evidence for totipotency.
The most common misapplication of the term totipotent in both the scientific and nonscientific literatures is to equate the ability of a cell to participate in an embryonic process with the ability to generate all of the structures of the body independently Fig. For example, the observation that stem cells will generate all or most of the tissues of the postnatal body after injection into an early stage embryo [ 22 , 23 ] or in a tetraploid complementation assay [ 24 ] is often misinterpreted as evidence that stem cells are totipotent [ 25—28 ].
Contribution of diploid and tetraploid cells to development. A In normal development, cells of the TE blue naturally become tetraploid or higher orders of ploidy and contribute predominantly to the placenta. ICM cells green remain diploid and contribute primarily to the structures of the postnatal body.
B Injection of diploid pluripotent stem cells with ICM-like properties into a morula-stage embryo prior to commitment of ICM cells results in stem cells contributing primarily to the ICM and therefore the structures of the postnatal body , with the cells of the embryo largely producing TE-derived structures.
C Injection of stem cells into a normal blastocyst-stage embryo in which the ICM has already formed results in a chimeric animal, with cells of the postnatal body derived both from the ICM and from the stem cells. D If embryos are electrically shocked at the two-cell stage to induce cell fusion, then an abnormally tetraploid embryo results. In most cases, the tetraploid embryo produces only TE derivatives, although live-born tetraploid mice [ ] and humans [ 33 , 34 ] have been reported.
Injection of diploid pluripotent stem cells at the blastocyst stage complements this defect, with stem cells producing most of the postnatal structures. ICM, inner cell mass. Yet, this assertion ignores the fact that in such experimental procedures, stem cells are merely participating in an embryonic process, not originating it. Clearly an unmanipulated embryo will produce a fully formed individual all on its own, without any assistance from stem cells Fig. The incorporation of injected cells into a preexisting embryo merely reflects the epigenetic state of pluripotent cells that biases them to contribute to the inner cell mass ICM lineage at both morula Fig.
Similarly, tetraploid embryos are still embryos, although with a significant defect that in most cases proves fatal. However, fully tetraploid mice frequently complete embryogenesis, and occasionally survive to live birth reviewed in Eakin and Behringer [ 32 ].
Similarly, there are reports of live-born, tetraploid humans [ 33 , 34 ], although mosaicism has not been strictly ruled out in most cases. In these assays Fig. Medically, it is reasonable to distinguish between transient structures that function only during gestation and structures that have functions after birth, since only the latter are the subject of medical intervention although with the rapidly expanding use of exutero intrapartum therapy, or EXIT, to treat fetal anomalies [ 36 ], this distinction may eventually become less medially relevant.
Like all embryonic structures, placenta and membranes are 1 generated by the embryo, 2 physically continuous with the embryo, 3 genetically identical to the embryo, and 4 critically required for the function and survival of the embryo as a whole ie, vital organs of the embryo itself. Many structures have similarly transient functions, including the lungs functioning only during postnatal life , the thymus functioning in a greatly diminished capacity at adult stages, compared with its function in the fetus , and the uterus functioning as a reproductive organ only between puberty and menopause.
Due to the purely gestational functions of extraembryonic structures, they are physically discarded at birth, but this is not fundamentally different from the atrophy of the ductus arteriosis a transient vascular structure that has essential functions only prenatally in the neonate, or the loss of primary teeth in childhood.
Scientific authors occasionally equate the ability of groups of cells to collectively generate a full developmental sequence with totipotency of individual cells within the group Fig. Dissociation and reaggregation of morula-stage blastomeres. A There is clear evidence for molecular differences between cells ie, specification as early as the four- to eight-cell stage [ 61—71 , , ]; yet, cell fates remain plastic.
B, C Following dissociation, it is likely that a combination of cell sorting arrows and respecification restores the original status of the embryo. D Once cell—cell contacts have been reformed, development proceeds from the blastocyst stage. F Outer cells remain competent to produce both ICM cells and additional TE cells curved arrows , as they do in normal development. G A combination of cell sorting, regeneration of ICM cells from outer cells, and potentially respecification of outer cells to an ICM lineage restores the original status of the embryo.
Primary cells isolated from a freshly dissociated embryos are likely to be a mixed population with different developmental capacities Fig. Zygotic transcription commences during the first cell cycle in both mouse [ 48—51 ] and human [ 52—59 ] embryos. While some studies have seen no difference in gene expression between early blastomeres [ 60 ], there is evidence from several groups suggesting that as early as the 4—8-cell stage, blastomeres have unique molecular properties [ 61—71 ] that translate into distinct developmental capabilities after dissociation and reaggregation [ 72 , 73 ].
Substantial evidence stretching back over 60 years indicates that when cells with distinct developmental states are aggregated, cell sorting plays a significant role in re-establishing the initial pattern [ 74 , 75 ]. In mice, cell sorting plays a significant role in the segregation of cells within normal cell [ 76 ] and cell embryos [ 77 ]. Therefore, the cell sorting that has been observed in some studies [ 37 ] is likely to reorganize the spatial relationships of blastomeres with limited developmental competency to reconstitute a full embryo Fig.
An important insight from cell aggregation experiments is that there is more than one way to make an embryo. Embryos produced by either fertilization or by cloning begin as a single-cell zygote that is by definition totipotent. To date, there is no evidence that groups of cells derived from any source other than a freshly dissociated morula-stage embryo can collectively generate a full developmental sequence on their own.
Even when freshly isolated ICM [ 79 ] or TE [ 80 , 81 ] from blastocyst-stage embryos are transferred to the uterus or other supportive locations, they do not develop as embryos. Groups of stem cells are also not totipotent. Yet, despite thousands of articles that describe the production of stem cell aggregates over the last three decades, there have been no reports of spontaneous generation of embryos from ESCs.
Similarly, there have been no reports of generating embryos from a combination of mES and trophoblast stem cells [ 84 ]. The failure of aggregated stem cell lines derived thus far to spontaneously form embryos is likely to reflect the fact that stem cell lines have a range of properties [ 85—87 ] that are not identical either to zygotes [ 88 , 89 ] or to cells that have been freshly isolated from embryos [ 43—47 ].
Scientific authors occasionally conflate expression of molecular markers characteristic of specific embryonic stages with the corresponding developmental capacities of cells at those stages. For example, several studies have determined that most or all mESCs cycle in and out of a unique transcriptional state that shares some elements in common with blastomeres at the two-cell 2C stage [ 14 , 90—92 ].
Cells in this 2C-like state lack pluripotency markers normally associated with the ICM, as do human zygotes and embryos at the two-cell stage [ 88 ].
Finally, some scientific authors suggest that the ability of stem cells to replicate limited aspects of normal embryonic development is evidence for totipotency, or something very close to it. For example, a number of studies have shown that ESC aggregates treated with specific signaling molecules exhibit some of the molecular cascades and cell behaviors observed during normal gastrulation [ 93—97 ].
Yet stem cell aggregates do not resemble organisms so much as they resemble tumors, which can also show a surprising degree of self-organization, producing well-formed teeth [ 98 ] and, even in one case, a remarkably normal eye [ 99 ]. Similarly, ESC aggregates [ , ] and tumors [ ] occasionally generate cystic structures that have some visual similarity to a blastocyst-stage embryo, which has led some authors to ask whether ESCs and tumors might also be embryos [ 9 , ].