Totipotency and Pluripotency
In scientific discourse, the terms totipotency and pluripotency are not used consistently. In classical embryology, totipotency describes the ability of a cell to develop into a complete organism under appropriate conditions. In the context of stem cell research, totipotency refers to the ability of a stem cell to differentiate into all kind of cell types, i.e. not only in embryonic tissue but also in extraembryonic tissues (e.g. placental tissue) and germ cells.
As stem cells continue to differentiate during the course of their development, they lose development potential. Thus, they soon lose the ability to develop into complete organisms, but initially retain the potential to differentiate into the full range of tissue types in the body. This stadium is known as pluripotency.
Various scientific findings of recent years intensify the ambiguity of the concept of totipotency. In 2009, scientists have shown that induced pluripotent stem cells (iPS cells) are also theoretically able to develop into a complete organism by using the procedure of tetraploid embryonic complementation (cf. module Tetraploid embryonic complementation). In addition, studies from 2012 and 2013 indicate that individual cells can oscillate between a pluripotent and totipotent status in the context of cell culture, and the extraction of so-called expanded potential stem cells (EPSCs) described in 2019 also leads to the question of whether the concept of totipotency must be narrowed down and defined on the basis of standardised criteria.
At present, it is not possible to experimentally prove or disprove the existence of totipotency. In fact, the totipotency of a cell can only be attributed retrospectively: an experimental demonstration would require letting a complete organism grow to maturity – against ethical concerns.
In the German Embryo Protection Act (§8 EschG), every totipotent human cell is accorded the same worthiness of protection as the human embryo. To this extent, the concept of totipotency has ethical and legal implications:
On the definition of the concept of a "totipotent cell" by lawmakers cf. § 8 of the German Embryo Protection Act (ESchG).
Günther, H. / Taupitz, J. / Kaiser, P. (2014): Embryonenschutzgesetz. Juristischer Kommentar mit medizinisch-naturwissenschaftlichen Grundlagen, Stuttgart: Kohlhammer. (German)
Cf. for ethical and legal implications of the definition and attribution of totipotency:
Denker, H. (2000): Embryonale Stammzellen und ihre ethische Wertigkeit. Aspekte des Totipotenz-Problems. In: Jahrbuch für Wissenschaft und Ethik 5, 291–304. (German)
Hermann, I. / Heyer, M. (2010): Wirklich Alleskönner? Bericht über Forschungsergebnisse und ausgesuchte ethische und rechtswissenschaftliche Fragen der Stammzellforschung. In: Spranger, Tade (Hrsg.): Aktuelle Herausforderungen der Life Sciences, 159–188. (German)
Baranzke, H. (2015): Der menschliche Embryo – Naturzweck oder Handlungszweck? Eine Kritik an Totipotenz und Potentialitätsargument in der Embryonenschutzdiskussion. In: Heinemann, Thomas / Dederer, Hans-Georg / Cantz, Tobias: Entwicklungsbiologische Totipotenz in Ethik und Recht: Zur normativen Bewertung von totipotenten menschlichen Zellen. Göttingen: Vandenhoeck & Ruprecht, 165–222. (German)
Schickl, H. / Braun, M. / Dabrock, P. (2017): Ways Out of the Patenting Prohibition? Human Parthenogenetic and Induced Pluripotent Stem Cells. In: Bioethics 31(5), 409–417. doi: 10.1111/bioe.12334 Online Version
For an overview of the phenomena of totipotency and pluripotency from a scientific point of view see:
Beier, H. M. (2001): Zur Problematik von Totipotenz und Pluripotenz. In: Bundesministerium für Bildung und Forschung. Humane Stammzellen. Perspektiven und Grenzen in der regenerativen Medizin. Stuttgart, New York, 55–70. (German)
Sgodda, S. (2015): Das Kriterium der Totipotenz aus naturwissenschaftlicher Perspektive. In: Heinemann, Thomas / Dederer, Hans-Georg / Cantz, Tobias: Entwicklungsbiologische Totipotenz in Ethik und Recht: Zur normativen Bewertung von totipotenten menschlichen Zellen. Göttingen: Vandenhoeck & Ruprecht, 13–55. (German)
Ott, M. (2015): Bewertung von artifiziellen „totipotenten“ Stammzellen aus naturwissenschaftlicher und medizinischer Sicht. In: Heinemann, Thomas / Dederer, Hans-Georg / Cantz, Tobias: Entwicklungsbiologische Totipotenz in Ethik und Recht: Zur normativen Bewertung von totipotenten menschlichen Zellen. Göttingen: Vandenhoeck & Ruprecht, 67–77. (German)
For the metioned scientific papers see:
Zhao, X. / Li, W. / Lv, Z. / Liu, L. / Tong, M. / Hai, T. / Hao, J. / Guo, C. / Ma, Q. / Wang, L. / Zeng, F. / Zhou, Q. (2009): iPS cells produce viable mice through tetraploid complementation. In: Nature 461, 86–90. doi: 10.1038/nature08267 Online Version
Abad, M. / Mosteiro, L. / Canamero, M. / Rayon, T. / Ors, I. / Grana, O. / Megías, D. / Dóminguez, O. / Martínez, D. / Manzanares, M. / Ortega, S. / Serrano, M. (2013): Reprogramming in vivo produces teratomas and iPS cells with totipotency features. In: Nature 502, 340–345. doi: 10.1038/nature12586 Online Version
Macfarlan, T. S. / Gifford, W. D. / Driscoll, S. / Lettieri, K. / Rowe, H. M. / Bonanomi, D. / Firth A. / Singer, O. / Trono, D. / Pfaff, S. L. (2012): Embryonic stem cell potency fluctuates with endogenous retrovirus activity. In: Nature 487, 57–63. doi: 10.1038/nature11244 Online Version
Gao, X. / Nowak-Imialek, M. / Xi, C. et al. (2019): Establishment of porcine and human expanded potential stem cells. In: Nature Cell Biology 21, 687–699. doi: 10.1038/s41556-019-0333-2 Online Version