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DOI: 10.1055/s-0035-1558183
Non-embryo-destructive Extraction of Pluripotent Embryonic Stem Cells: Implications for Regenerative Medicine and Reproductive Medicine
Embryonenerhaltende Gewinnung pluripotenter Stammzellen: Implikationen für die regenerative Medizin und die ReproduktionsmedizinPublication History
received 02 June 2015
revised 12 August 2015
accepted 20 August 2015
Publication Date:
21 December 2015 (online)
Abstract
On August 1, 2013, the German Patent and Trademark Office issued a patent for the “Non-embryo-destructive extraction of pluripotent embryonic stem cells, stem cells obtained by this process and their uses” (DE 10 2004 062 184 B4). The patent document describes a non-embryo-destructive process to harvest embryonic stem cells from the inner cell mass (ICM) during the blastocyst development stage. The patent application was filed with the German Patent Office in Munich on December 23, 2004 and the patent claim was published in 2006. The patent was granted on August 1, 2013. Processing the patent application was a lengthy affair due to the fact that, for a long time, the prevailing opinion in Germany was that genetic screening of embryos (preimplantation genetic diagnosis) was prohibited under the German Embryo Protection Act (ESchG). A ruling by the German Federal Court in 2010 proved this opinion to be false. Animal studies have provided the evidence that the described procedure is technically feasible; healthy offspring were born after stem cells were harvested from the blastocyst and stored. We report here on a technique for the non-embryo-destructive extraction of pluripotent embryonic stem cells together with potential future applications for stem cells harvested in this manner.
Zusammenfassung
Am 1. August 2013 wurde vom Deutschen Patent- und Markenamt das Patent für die Patentschrift „Embryonenerhaltende Gewinnung pluripotenter embryonaler Stammzellen, derart gewonnene Stammzellen und Verwendung derselben“ (DE 10 2004 062 184 B4) erteilt. Das vorliegende Patent beschreibt ein Verfahren zur embryonenerhaltenden Gewinnung embryonaler Stammzellen aus der inneren Zellmasse (ICM) im Entwicklungsstadium der Blastocyste. Es wurde am 23. 12. 2004 beim Deutschen Patentamt in München angemeldet und 2006 als Patentanspruch offengelegt, also veröffentlicht. Rechtswirksam erteilt wurde das Patent am 1. 8. 2013. Die lange Bearbeitungsfrist ergab sich u. a. dadurch, dass in Deutschland lange Zeit die Meinung vorherrschte, dass genetische Untersuchungen am Embryo (Präimplantationsdiagnostik) nach dem Embryonenschutzgesetz (ESchG) verboten seien, was sich erst nach einem Urteil des Bundesgerichtshof im Jahre 2010 als unzutreffend erwies. Der Nachweis, dass das dargestellte Verfahren auch technisch umsetzbar ist, erfolgte im Tierversuch, nach Stammzellasservation wurde aus den Blastozysten eine gesunde Nachkommenschaft geboren. Im Artikel werden die Techniken der embryonenerhaltenden Gewinnung pluripotenter embryonaler Stammzellen beschrieben und die potenziellen Möglichkeiten einer Anwendung aufgezeigt.
Key words
stem cell extraction - embryo-preserving - preimplantation genetic diagnosis (PIGD) - preimplantation therapy (PIT)Schlüsselwörter
Stammzellgewinnung - embryonenerhaltend - Präimplantationsdiagnostik (PID) - Präimplantationstherapie (PIT)-
References
- 1 DPMAregister. DE 10 2004 062 184.5.. Online: https://register.dpma.de/DPMAregister/pat/register?AKZ=1020040621845 last access: 20.04.2015
- 2 Evans MJ, Kaufmann MH. Establishment in culture of pluripotential cells from mouse embryo. Nature 1981; 292: 154-156
- 3 Thomson JA, Itskovitz-Eldor J, Shapiro SS et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145-1147
- 4 Heins N, Englund MC, Sjöblom C et al. Derivation, characterization, and differentiation of human embryonic stem cells. Stem Cells 2004; 22: 367-376
- 5 Mateizel I, De Temmerman N, Ullmann U et al. Derivation of human embryonic stem cell lines from embryos obtained after IVF and PGD for monogenic disorders. Mol Hum Reprod 2006; 21: 503-511
- 6 Zhang X, Stoikovic P, Przyborski S et al. Derivation of human embryonic stem cells from developing and arrested embryos. Stem Cells 2006; 24: 2669-2676
- 7 Amit M, Itskovitz-Eldor J. Sources, derivation and culture of human embryonic stem cells. Semin Reprod Med 2006; 24: 298-303
- 8 Piotrowska K, Wianny F, Pedersen RA et al. Blastomeres arising from the first cleavage division have distinguishable fates in normal mouse development. Development 2001; 128: 3739-3748
- 9 Smith AG. Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol 2001; 17: 435-462
- 10 Pickering SJ, Braude PR, Burns CJ et al. Preimplantation genetic diagnosis as a novel source of embryos for stem cell research. Reprod Biomed Online 2003; 7: 353-364
- 11 Cowan CA, Klimanskaya I, McMahon MS et al. Derivation of embryonic stem-cell lines from human blastocysts. N Engl J Med 2004; 350: 1353-1356
- 12 Verlinsky Y, Streichenko N, Kukharenko V et al. Human embryonic stem cell lines with genetic diorders. Reprod Biomed Online 2005; 10: 105-110
- 13 Hug K. Sources of human embryos for stem cell research: ethical problems and their possible solutions. Medicina (Kaunas) 2005; 41: 1002-1010
- 14 Evans M. Ethical sourcing of human embryonic stem cells – rational solutions?. Nat Rev Mol Cell Biol 2005; 6: 663-667
- 15 Feki A, Bosman A, Dubuisson JB et al. Derivation of the first Swiss human embryonic stem cell line from a single blastomere of an arrested four-cell stage embryo. Swiss Med Wkly 2008; 138: 540-550
- 16 Chung Y, Klimanskaya I, Becker S et al. Embryonic and extraembryonic stem cell lines derived from single mouse blastomeres. Nature 2006; 439: 216-219
- 17 Klimanskaya I, Chung Y, Becker S et al. Human embryonic stem cell lines derived from single blastomeres. Nature 2006; 444: 481-485
- 18 Klimanskaya I, Chung Y, Becker S et al. Derivation of human embryonic stem cells from single blastomeres. Nat Protoc 2007; 2: 1963-1972
- 19 Chung Y, Klimnaskaya I, Becker S et al. Human embryonic stem cell lines generated without embryo destruction. Cell Stem Cell 2008; 2: 113-117
- 20 Kelly SJ. Studies of the developmental potential of 4- and 8-cell stage blastomeres. J Exp Zool 1977; 200: 365-376
- 21 Pedersen RA. Potency, Lineage and Allocation in Preimplantation Mouse Embryos. In: Rossant J, Pedersen RA, eds. Experimental Approaches to mammalian embryonic Development. New York, USA: Cambridge University Press; 1986: 3-33
- 22 Geens M, Mateizel I, Sermon K et al. Human embryonic stem cell lines derived from single blastomeres of two 4-cell stage embryos. Hum Reprod 2009; 24: 2709-2717
- 23 Giritharan G, Ilic D, Gormley M et al. Human embryonic stem cells derived from embryos at different stages of development share similar transcription profiles. PLoS ONE 2011; 6: e26570
- 24 Cenariu M, Pall E, Cernea C et al. Evaluation of bovine embryo biopsy techniques according to their ability to preserve embryo viability. J Biomed Biotech 2012; DOI: 10.1155/2012/541384.
- 25 Fong CY, Richards M, Bongso A. Unsuccessful derivation of human embryonic stem cell lines from pairs of human blastomeres. Reprod Biomed Online 2006; 13: 295-300
- 26 Johnson MH, McConell JM. Lineage allocation and cell polarity during mouse embryogenesis. Semin Cell Dev Biol 2004; 15: 573-581
- 27 Ilic D, Giritharan G, Zdravkovic T et al. Derivation of human embryonic stem cell lines from biopsied blastomeres on human feeders with minimal exposure to xenomaterials. Stem Cell Dev 2009; 18: 1343-1350
- 28 Klimanskaya I. Embryonic stem cells from blastomeres maintaining embryo viability. Semin Reprod Med 2013; 31: 49-55
- 29 Bundesgerichtshof, 5. Strafsenat. Urteil vom 6. Juli 2010: 5 StR 386/09.
- 30 Dittrich R, Lotz L, Würfel W et al. Offspring after embryo-preserving biopsy of the embryoblast with standard ICSI equipment in mouse blastocysts. In Vivo 2011; 25: 935-939
- 31 Bianco P, Robey PG, Simmons PJ. Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2008; 4: 313-319
- 32 Snykers S, De Kock J, Rogiers V et al. In vitro differentiation of embryonic and adult stem cells into hepatocytes: state of the art. Stem Cells 2009; 27: 577-605
- 33 Gyurkocza B, Rezvani A, Storb RF. Allogeneic hematopoietic cell transplantation: the state of the art. Exp Rev Hematol 2010; 3: 285-299
- 34 Farge D, Labopin M, Tyndall A et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 yearsʼ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Disease. Haematologica 2010; 95: 284-292
- 35 Tobler KJ, Zhao Y, Ross R et al. Comparative genomic hybridization microarray (aCGH) analysis of DNA isolated from blastocoels fluid from 26 blastocysts. Fertil Steril 2014; 101 (Suppl.) e4
- 36 Tobler KJ, Zhao Y, Ross R et al. Blastocoel (BF) harbours embryonic DNA that may result from the marginalization of aneuploid cells during embryogenesis. Fertil Steril 2014; 102 (Suppl.) e205
- 37 Tobler KJ, Zhao Y, Ross R et al. The potential use of blastocoels fluid (BF) from expanded blastocysts as a less invasive form of embryo biopsy for preimplantation genetic testing. Fertil Steril 2014; 102 (Suppl.) e183-e184
- 38 Würfel W. Der frühe Embryo – Netzwerke autologer, maternaler und iatrogener Regulation. Gynäkologische Endokrinologie 2015; 13: 92-97
- 39 Polzin VJ, Anderson DL, Anderson GB et al. Production of sheep-goat chimeras by inner cell mass transplantation. J Animal Sci 1987; 65: 325-330
- 40 Zheng YL, Jiang MX, OuYang YC et al. Production of mouse by inter-strain inner cell mass replacement. Zygote 2005; 13: 73-77
- 41 Murakami M, Ferguson CE, Perez O et al. Transfer of inner cell mass cells derived from bovine nuclear transfer embryos into the trophoblast of bovine in vitro-produced embryos. Cloning Stem Cells 2006; 8: 51-60
- 42 Li BL, Chang KH, Wang PR et al. Trisomy correction in Down syndrome induced pluripotent stem cells. Cell Stem Cell 2012; 5: 615-619
- 43 Jiang J, Jing Y, Cost GJ et al. Translation dosage compensation to trisomy 21. Nature 2013; 500: 296-300
- 44 Disteche CM. How to correct chromosomal trisomy. Cell Res 2013; 23: 1345-1346
- 45 Kay MA. State-of-the art gene based therapies: the road ahead. Nature Rev Genet 2011; 12: 316-328
- 46 Mikkers HM, Freund C, Mummery CL et al. Cell replacement therapies: is it time to reprogram?. Hum Gene Ther 2014; 25: 866-874