Creation of Chimera

The artificial creation of chimera and hybrids by combination of the human species with another species has triggered special controversies. The object of such controversies are embryos generated by the injection of a human cell nucleus into a previously enucleated oocyte of an animal, or animal embryos in which human stem cells evolve in vivo. In the case of the enucleated animal egg cell, the embryo produced contains a small number of animal cells, in the case of genetically modified animal embryos with introduced human stem cells, the embryo produced contains a small number of human cells.

In the long term, there is hope that the intermixture of cells across species will allow the creation of organs for transplantation and an improved cultivation and differentiation of stem cells in human medicine. The differentiation of human stem cells into different cell types in particular has hitherto succeeded only partly outside the embryo, i.e. under laboratory conditions. The injection of human iPS cells into animal embryos, thus, promises possible improvements in the development of patient-specific differentiated stem cells in vivo and, long-term, the production of patient-specific transplantation organs. Beside these central issues of research on so called human-animal hybrids and chimera, there is hope that a deeper understanding of fundamental human development processes such as embryogenesis, and an avoidance of the ‘use’ of human oocytes will result from such experiments.

The procedures set out for such aims are currently experimental. This is a result of difficulties finding a ‘host species’ in which human stem cells can develop in sufficient amount and similar speed. In January 2017, Juan Carlos Izpisúa Belmonte and his team showed that, after injecting human iPS cells in swine embryos, the cells formed into precursor cells of human organs, such as liver and heart cells, in the course of the first four weeks of embryo development. The development of chimera embryos was cancelled because of ethical concerns four weeks after introducing them into the uterus.

In January 2017, a research team lead by Hiromitsu Nakauchi further published the results of a study in which mice pancreas were produced in rat embryos. Murine stem cells were injected into rat embryos for this purpose. The genetic sequence responsible for the creation of the pancreas was also ‘deactivated’ with the genetic scissor CRISPR-Cas9. As a result, mice pancreas developed inside the rat embryos that, in turn, developed into viable rats. After the transplantation of tissue taken from these pancreas into mice that had previously been induced with diabetes, therapeutic successes were achieved that showed a regained capability to create insulin.

After the announcement of Hiomitsu Nakauchi’s research team in summer 2019 saying that they plan to gradually develop the animal embryos supplemented with human iPS cells beyond the 14th day, but without letting them be delivered until birth, the debate concerning ethical implication was rekindled. The announcement was preceded by the liberalisation of the Japanese regulation, which allows the so called chimeras to be carried until full term. Shortly thereafter, the Spanish stem cell researcher Juan Carlos Izpisúa Belmonte said that he had carried out similar experiments with human stem cells on primate embryos (macaques). As macaques are genetically more closely related to humans, such experiments could lead to a better development of the human stem cells but at the same time the risk of unintentional involvement of human cells in other areas of the developing embryo may rise. Ethical concerns are primarily directed to the potential ‘migration’ of human stem cells within animal embryos and the consequent development of ‘human’ features, for example with respect to the nervous system in the individuals thus created.

For the experiments with human stem cells and pig embryos led by the research team of Juan Carlos Izpisúa Belmonte see:

Wu, J. / Platero-Luengo, A. / Sakurai, M. / Sugawara, A. / Gil, M. A. / Yamauchi, T. / Suzuki, K. / Bogliotti, Y. S. / Cuello, C. / Valencia, M. M. / Okumura, D. / Luo, J. / Vilarino, M. / Parrilla, I. / Soto, D. A. / Martinez, C. A. / Hishida, T. / Sánchez-Bautista, S. / Martinez-Martinez, M. L. / Wang, H. / Nohalez, A. / Aizawa, E. / Martinez-Redondo, P. / Ocampo, A. / Reddy, P. / Roca, J. / Maga, E. A. / Esteban, C. R. / Berggren, T. W. / Delicado, E. N. / Lajara, J. / Guillen, I. / Guillen, P. / Campistol, J. M. / Martinez, E. A. / Ross, P. J. / Izpisúa Belmonte, J. C. (2017): Interspecies Chimerism with Mammalian Pluripotent Stem Cells. In: Cell 168, 473–486. doi: 10.1016/j.cell.2016.12.036. Online Version

For the experiments with murine stem cells and rat embryos led by the team of Hiromitsu Nakauchi see:

Yamaguchi, T. / Sato, H. / Kato-Itoh, M. / Goto, T. / Hara, H. / Sanbo, M. / Mizuno, N. / Kobayashi, T. / Yanagida, A. / Umino, A. / Ota, Y. / Hamanaka, S. / Masaki, H. / Rashid, S. T. / Hirabayashi, M. / Nakauchi, H. (2017): Interspecies organogenesis generates autologous functional islets. In: Nature 542, 191–196. doi: 10.1038/nature21070 Online Version

For Nakauchi's research project on "human-animal embryos", see:

Cyranoski, D. (2019): Japan approves first human-animal embryo experiments. In: Nature [published online July 26, 2019]. doi: 10.1038/d41586-019-02275-3 Online Version

For the experiments with human stem cells and primate embryos by the research team led by Juan Carlos Izpisúa Belmonte, see: 

Tan, T. / Wu, J. / Si, C. / Dai, S. / Zhang, Y. / Sun, N. / Zhang, E. / Shao, H. / Si, W. / Yang, P. / Wang, H. / Chen, Z. / Zhu, R. / Kang, Y. / Hernandez-Benitez, R. / Martinez Martinez, L. / Nuñez Delicado, E. / Berggren, W. T. / Schwarz, M. / Ai, Z. / Li, T. / Deng, H. / Esteban, C. R. / Ji, W. / Niu, Y. / Izpisúa Belmonte, J. C. (2021): Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo. In: Cell 184 (8), 2020–2032.e14. doi:10.1016/j.cell.2021.03.020. Online Version 

For further information about the current state of research, possibilities and limitations of the creation of chimera see:

De Los Angeles, A. / Pho, N. / Redmond, E. D. (2018): Generating Human Organs via Interspecies Chimera Formation: Advances and Barriers. In: The Yale Journal of Biology and Medicine 91(3), 333–342. Online Version

Garry, D. J. / Garry, M. G. (2021): Interspecies chimeras as a platform for exogenic organ production and transplantation. In: Experimental Biology and Medicine 246(16), 1838–1844. Online Version

Wu, J. / Greely, H. T. / Jaenisch, R. / Nakauchi, H. / Rossant, J. / Izpisúa Belmonte, J. C. (2016): Stem cells and interspecies chimaeras. In: Nature 540(7631), 51–59. doi: 10.1038/nature20573 Online Version 

For the ethical analysis of research on so called human-animal hybrids and chimera see for example:

Camporesi, S. / Boniolo, G. (2008): Fearing a non-existing Minotaur? The ethical challenges of research on cytoplasmic hybrid embryos. In: Journal of Medical Ethics 34, 821–825. doi:10.1136/jme.2008.024877 Online Version 

Mann, S. P. / Sun, Rosa / Hermerén, G. (2019): Ethical Considerations in Crossing the Xenobarrier. In: Hyun, I. / De los Angeles, A. (Hrsg.): Chimera Research. Methods in Molecular Biology. New York: Humana Press, 175–193. doi: 10.1007/978-1-4939-9524-0_12

German Ethics Council (2011): Human-animal mixtures in research. Opinion. Online Version

Wird geladen