Prompt: Solving complex questions often calls for expertise in many fields. Describe how multidisciplinary collaborations and approaches (or future opportunities for them) have already or will in the future impact your own training, research, or career. (https://laskerfoundation.org/the-2022-lasker-essay-contest-is-now-open/)
https://www.cell.com/pictureshow/organoids
It Takes a Village to ‘Raise’ a Mini-Organ
The ability of a single-cell zygote to develop into an adult human is truly one of the most captivating and complex biological phenomena. This is enabled by a peculiar population of cells found in a developing embryo called pluripotent stem cells (PSCs). In Latin, ‘pluri’ means many, and ‘potent’ means ‘have the power’; these remarkable cells have a ‘super-power’ that allows them to develop into many different cells, tissues, and organs that makes up the human body. Within the past two decades, scientific researchers, such as myself, have embarked on the quest to tap into the tremendous potential of PSCs to generate different types of cells in the lab. Today, we can readily produce almost any cell type in the human body from PSCs. Recently, the stem cell community conceptualized and popularized the innovative idea of creating not just cells, but miniature organs (‘mini-organs’, or ‘organoids’) from PSCs in a dish. However, because of the sheer structural and architectural complexity of human organs, the construction of organoids that recapitulates organ physiology from PSCs is no simple task. Our endeavor to successfully develop organoids from PSCs undoubtedly requires immense levels of multi-disciplinary collaboration and communication.
‘Mini-hearts’ that beat (1) or ‘mini-brains’ that are capable of neuronal activity (2,3), which used to only be fantasies portrayed in sci-fi films, have already become a reality, thanks to the combined efforts of developmental, molecular, and stem cell biologists. First, developmental biologists lay the foundation and study organs development from PSCs during organogenesis. Then, molecular and stem cell biologists, like myself, build upon that foundation and create conditions that mimic developmental processes, and we formulate biological cocktails of proteins and small compounds that provide the appropriate signals for PSCs to grow and develop into organoids.
“That sounds like something from Frankenstein!” is a typical response whenever I tell someone that I grow organoids in the lab. But, unlike Victor Frankenstein, who built a living creature in his attic, our goal is to build organoids to study human development and disease. Through collaborative efforts between organoid scientists and clinicians, we have been able to successfully utilize organoids to model developmental and genetic disorders, as well as cancer. Additionally, organoids have remarkable potential in drug testing and even personalized medicine, and future partnerships and collaborations between organoid researchers, pharmacologists, physicians, and surgeons will be necessary to achieve these goals.
Organoid researchers have made great strides in the field, and today, we can construct organoids that share many striking resemblances to actual human organs. However, the complexity of these organoids still falls short of their naturally-occurring counterparts. They lack extensive blood vessel networks that can deliver blood and nutrients from the circulatory system and they lack other critical cell types such as nerves and immune cells. Lastly, they lack interactions with other organs and thus, are void of inter-organ features.
The challenges of organoid development have prompted organoid researchers to realize that they will need expertise beyond developmental, molecular, and stem cell biology in order to overcome these barriers. Therefore, organoid researchers have since sought collaborations with scientists of different disciplines to work towards building the ‘next-generation’ of organoids (4). Bioengineers design platforms that permit complicated organoid construction. Also, material scientists create suitable biomaterials that support complex and large organoid growth. And, bioinformaticians utilize computational tools to dissect the organoids’ cellular and molecular constituents. Last, but certainly not least, developmental and molecular biologists, like myself, pattern and grow these organoids, and later, perform molecular and functional tests on them. Due to these interdisciplinary collaborations, further progress has been and is continuing to be made. In the field of neurobiology, two brain region-specific organoids were fused to form ‘assembloids,’ complex organoids that display remarkable neuronal connections and cell-cell communication (5). Also, intricate hepato-biliary-pancreatic organoids have been constructed, which mimic the natural development of the liver, bile ducts, and pancreas (6). And, recently, an advanced technology called ‘organoids-on-chip’ was developed, which grows organoids in separate chambers on a singular device that controls the microenvironment (7). Collectively, these innovative and state-of-the-art organoids are made possible by multi-disciplinary collaborations.
It truly takes a village to ‘raise’ a human organoid. The fact that organoid researchers can no longer work independently (like Victor Frankenstein), but must work collaboratively with other scientists in order to successfully build mini-organs, not only reflects the complexities of human organs but also exemplifies the significance of inter-disciplinary cooperation. Globally, ‘organoid centers’ that amalgamate scientists from different disciplines are emerging (8), further signifying the importance of this integrative and collaborative approach. The multi-disciplinary collaboration will continue to play a critical role in my scientific career as a stem cell researcher, and as I embark on my PhD journey, I am excited to be a part of this ‘organoid task force’ that will bring organoid research and organoid-based therapies to the forefront of human medicine and biomedical applications.
References
1. Hofbauer, P. et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell 184, 3299-3317.e22 (2021).
2. Chiaradia, I. & Lancaster, M. A. Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo. Nat Neurosci 23, 1496–1508 (2020).
3. Trujillo, C. A. et al. Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development. Cell Stem Cell 25, 558-569.e7 (2019).
4. Takebe, T. & Wells, J. M. Organoids by design. Science364, 956–959 (2019).
5. Miura, Y. et al. Generation of human striatal organoids and cortico-striatal assembloids from human pluripotent stem cells. Nat Biotechnol 38, 1421–1430 (2020).
6. Koike, H. et al. Engineering human hepato-biliary-pancreatic organoids from pluripotent stem cells. Nat Protoc16, 919–936 (2021).
7. Yin, F. et al. HiPSC-derived multi-organoids-on-chip system for safety assessment of antidepressant drugs. Lab Chip 21, 571–581 (2021).
8. Takebe, T., Wells, J. M., Helmrath, M. A. & Zorn, A. M. Organoid Center Strategies for Accelerating Clinical Translation. Cell Stem Cell 22, 806–809 (2018).
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