Alternative methods for the derivation of human embryonic stem cells

In the years 2006 and 2007, a research team led by Robert Lanza published several studies on a method which enables the derivation of human embryonic stem cells without destroying the embryo. During the so-called blastomere extraction, a single blastomere cell is taken from an embryo at the eight-cell stage by using a biopsy technique which is also applied in preimplantation genetic diagnosis (PGD). Then, in order to obtain stem cells from the cell, it is cultured in a stem cell colony in the test tube and stimulated to divide. In later experiments, it was also possible to obtain stem cells without cultivation in already existing stem cell colonies. Biopsied donor embryos are not destroyed during the process and remain basically developable. However, they are often slowed in their further development and can be damaged during cell collection.

A similar method to derive embryonic stem cells without destroying the embryo is based on single cells of the inner cell mass (ICM) at the development stage of the blastocyst. Hence, this method aims at a later stage of embryonic development, namely days 5 and 6, at which different cell types have already differentiated and are thus no longer considered totipotent. Since single cells at the eight-cell stage can still be totipotent and the removal of totipotent cells from an embryo is prohibited according to § 2 (1) of the German Embryo Protection Act (ESchG), the first described method of blastomere extraction is not permitted in Germany (cf. Preimplantation Genetic Diagnosis, Legal aspects). However, the removal of pluripotent cells at the later blastocyst stage is also legally controversial, as a discussion between Dittrich and Faltus shows. Foremost, they criticise that the embryo, while not destroyed in either procedure, is still used for the purpose of a third party. The fact that the biopsy techniques require a high degree of technical skills also prevents establishing the procedures. 

Another method by which stem cells are derived from arrested embryos appears to be ethically less questionable. Arrested embryos are produced in more than half of all in vitro fertilization (IVF) treatments. After several successful cell divisions, there is a natural abandonment of the development in many fertilized oocytes due to chromosomal aberration. If the arrested development lasts more than 24 hours, the embryos are no longer viable and therefore considered “dead”. In a study by the research team led by Miodrag Stojkovic, it was shown that under the correct in vitro conditions it is possible to derive pluripotent embryonic stem cell lines from late arrested embryos. Although arrested embryos are no longer capable of cell division and development, they can still contain single viable cells that can be used for the derivation of stem cells. The scientists showed that the procedure is technically feasible, but not yet sufficiently efficient. It must also be clarified whether stem cells obtained in this way are equivalent to stem cells obtained from fully developed embryos. 

The alternative methods for the derivation of embryonic stem cells just described have not been used widely so far. In addition to technical requirements, the remaining reservations of lawmakers (e.g. in Germany) and the mostly low efficiency of the techniques, the lack of use is mainly due to the accessibility of already existing embryonic stem cell lines. Besides, the established and comparatively efficient techniques with which the development of the embryos is interrupted are allowed in many countries on so-called surplus embryos from IVF treatments.

An overview of alternative methods for obtaining pluripotent stem cells is given by M. L. Condic:

Rao, M. / Condic, M. L. (2008): Issues in Development. Alternative Sources of Pluripotent Stem Cells: Scientific Solutions to an Ethical Dilemma. In: Stem Cells and Development 17, 1–10. doi: 10.1089/scd.2008.0013 Online Version

The studies mentioned in the text:

Klimanskaya, I. / Chung, Y. / Becker, S. / Lu, S. / Zdravkovic, T. / Ilic, D. / Genbacev, O. / Fisher, S. / Krtolica, A. / Lanza, R. (2007): Human Embryonic Stem Cell Lines Generated without Embryo Destruction. In: Cell Stem Cell Correspondence 2(2), 113–117. doi: 10.1016/j.stem.2007.12.013 Online Version 

Dittrich, R. / Beckmann, M. W. / Würfel, W. (2015): Non-embryo-destructive Extraction of Pluripotent Embryonic Stem Cells: Implications for Regenerative Medicine and Reproductive Medicine. In: Geburtshilfe und Frauenheilkunde 75, 1239–1242. doi: 10.1055/s-0035-1558183 Online Version 

Faltus, T. / Storz, U. (2016): Response to: Dittrich et al.: Non-Embryo-Destructive Extraction of Pluripotent Embryonic Stem Cells – Overlooked Legal Prohibitions, Professional Legal Consequences and Inconsistencies in Patent Law. In: Geburtshilfe und Frauenheilkunde 76, 1302–1307. doi: 10.1055/s-0042-110400 Online Version 

Dittrich, R. / Beckmann, M. W. / Würfel, W. (2016): Reply to “Response to: Dittrich et al.: Non-Embryo-Destructive Extraction of Pluripotent Embryonic Stem Cells – Overlooked Legal Prohibitions, Professional Legal Consequences and Inconsistencies in Patent Law”. In: Geburtshilfe und Frauenheilkunde 76, 1308–1309. doi: 10.1055/s-0042-116545 Online Version 

Zhang, X. / Stojkovic, P. / Przyborski, S. / Cooke, M. / Armstrong, L. / Lako, M. / Stojkovic, M. (2006): Derivation of human embryonic stem cells from developing and arrested embryos. In: Stem Cells 24(12), 2669–2676. doi:10.1634/stemcells.2006-0377 Online Version 

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