“The elementary parts of all tissues are formed of cells in an analogous, though very diversified manner, so that it may be asserted, that there is one universal principle of development for the elementary parts of organisms, however different, and that this principle is the formation of cells.” – Theodor Schwann

Organoids are essentially microcosms of organs, recapitulating organ function.   Organoids enable the study of organs in 3D models, allowing modification of genetic and environmental factors that influence ultimate function.[1] Although organoids are now highly researched, scientists have considered and experimented with their creation since the beginning of the 20^th century.[2]

Already, organ and disease modeling with organoids have yielded promising advances in regulating genes involved in cystic fibrosis, retinal diseases, carcinogenesis and metastasis, diabetes, and kidney disease. CRISPR can correct genetic defects via organoids to help prevent or treat disease.[3] Biomedical research in vitro and in vivo using organoids can also potentially be used for diagnostics, precision and personalized medicine, tissue regeneration and transplantation. As with CRISPR, ethical considerations will be vigorously debated as demand for the technology increases and clinical trials progress.[4] [5] [6]

Brain Organoid. Credit: Collin Edington and Iris Lee, Koch Institute MIT. CC BY-NC-ND [16]

Derived from stem cells, organoids are propagated in culture in three-dimensional cell clusters for later experimentation.[7] Their stem cell origin enables them to develop into a multitude of different organoid types, creating an environmental microcosm of the organ of interest.[8] In this fashion, organoids are capable of regenerating and modeling development and disease in organs such as the liver, pancreas, lung, intestine, stomach, prostate, breast, and brain.[9] [10] [11] [12] [13] Organoids develop upon the culture of pluripotent cells – meaning that organoids may develop into any of a variety of different mature cell types when placed in an amenable environment for growth- hES (human embryonic stem) and hiPS (human induced pluripotent stem) cells. [14]

As organoid technology advances, clinical and research teams must consider how they will adeptly weigh ethical concerns with cost, informed consent, quality of patient care and a host of other relevant issues. For instance, the National Institutes of Health Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative is currently supporting a two-year grant in partnership with the Massachusetts Institute of Technology (MIT) to study the interface between ethics and neurology – neuroethics – in the field of organoid research. Renowned researchers in the fields of neurology and Genetics such as Paola Arlotta, PhD, and George Church, PhD, will join Insoo Hyun, PhD, in this organoid neuroethics research collaborative.[15]

Dorkina Myrick, MD, PhD, MPP, is a physician-scientist trained at the National Institutes of Health in Bethesda, Maryland. She is currently a JD candidate at the Boston University School of Law.

References:

[1] Shamir, E.R., and A.J. Ewald. 2014. Three-dimensional organotypic culture: Experimental models of mammalian biology and disease. Nat. Rev. Mol. Cell Biol.15:647–664.

[2] Marina Simian and Mina J. Bissell. Organoids: A historical perspective of thinking in three dimensions. J Cell Biol Jan 2017, 216 (1) 31-40. 28 December 2016. Online: http://jcb.rupress.org/content/early/2016/12/27/jcb.201610056. Retrieved 15 March 2018.

[3] Aliya Fatehullah, Si Hui Tan, and Nick Barker. Organoids as an in vitro model of human development and disease. 25 February 2016. Nature Cell Biology. volume 18, pages 246–254 (2016). Online: http://www.nature.com/ncb/journal/v18/n3/full/ncb3312.html. 15 March 2018.

[4] Id.

[5] Michael A. Cantrell and Calvin J. Kuo. Organoid modeling for cancer precision medicine. Genome Med. 2015; 7(1): 32.

Online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377844/.

[6] Annelien L. Bredenoord, Hans Clevers, Juergen A. Knoblich. Human tissues in a dish: The research and ethical implications of organoid technology. Science.Vol. 355, Issue 6322. 20 Jan 2017. Online: http://science.sciencemag.org/content/355/6322/eaaf9414.

[7] Id. at Organoids: A historical perspective of thinking in three dimensions.

[8] Meritxell Huch and Bon-Kyoung Koo. Modeling mouse and human development using organoid cultures. Development. vol. 142: 3113-3125. 2015. Online: http://dev.biologists.org/content/142/18/3113. Retrieved 15 March 2018.

[9] Marius Ader and Elly M Tanaka. Modeling human development in 3D culture. Current Opinion in Cell Biology. Volume 31, December 2014, Pages 23-28. Online: http://www.sciencedirect.com/science/article/pii/S0955067414000842. Retrieved 15 March 2018.

[10] Broutier, Laura et al. Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. Nature Protocols volume 11, pages 1724–1743 (2016). Online: http://www.nature.com/nprot/journal/v11/n9/full/nprot.2016.097.html. Retrieved 15 March 2018.

[11] Dye, B.R. et al. Lung organoids. Nature Methods. volume 12, p. 388. 29 April 2015. Online: http://www.nature.com/nmeth/journal/v12/n5/full/nmeth.3378.html. Retrieved 15 March 2018.

[12] Id. at Modeling mouse and human development using organoid cultures.

[13] Stuart M. Chambers, JasonTchieu, Lorenz Studer. Build-a-Brain. Volume 13, Issue 4, 3 October 2013, Pages 377-378. Online: http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(13)00410-4. Retrieved 15 March 2018.

[14] Shamir,  E.R., and A.J. Ewald. 2014. Three-dimensional organotypic culture: Experimental models of mammalian biology and disease. Nat. Rev. Mol. Cell Biol.15: 647–664.

[15] A Human Brain Model in a Petri Dish? Press Release. Case Western Reserve University School of Medicine. Online: 16 October 2018. http://casemed.case.edu/cwrumed360/news-releases/release.cfm?news_id=1508&news_category=8. Retrieved 7 January 2019.

[16] Image: A brain organoid comprised of neural progenitor cells which recapitulate brain structure and function as part of the “human-on-a-chip” project. Wellcome Image Collection.