Think of a small, living piece of bodily tissue, no bigger than a bean, thriving in a petri dish. Although it might sound unreal, this science is a reality! These mini, self-organizing structures are reforming how we see human anatomy, biology, and disease. We’ll be diving into the universe where science meets imagination, and innovation. These miniature miracles are leading to medical breakthroughs that are leaving their mark on history.
Mini organs represent a biomedical frontier opening new avenues for regenerative medicine and developmental biology. Organoids are three‐dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self‐organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts [1].
A section of a brain organoid after three months of culture. The different colors mark distinct types of cells, highlighting the organoid's structural complexity. (Image courtesy of the Arlotta laboratory.) [2]
How are organoids made?
Organoids are produced from stem cells—versatile cells in the body that can differentiate into various types of tissue. There are many different kinds of stem cells. Organoids have been generated from both pluripotent stem cells (PSCs) and adult stem cells (ASCs) by mimicking the biochemical and physical cues of tissue development and homeostasis [3].
To create these organoids, scientists embed PSCs into an extracellular mix (A massive web of proteins and other molecules that envelop, support, and structurize cells and tissues in the body.) like Matrigel.
There are different types of organoids; ranging from neural to intestinal. Neural organoids, also known as cerebral organoids, are hPSC-derived three-dimensional in vitro culture systems that recapitulate the developmental processes and organization of the developing human brain. These ‘mini-brains’ provide a physiologically relevant in vitro 3D brain model for the study of neurological development and disease processes that are unique to the human nervous system. They have important applications in studying human brain development and neurological disorders such as autism, schizophrenia or brain defects caused by Zika virus infection [4].
Pluripotent Stem Cells, otherwise known as Human pluripotent stem cells (hPSCs) are cells that possess the capacity to self-renew and to differentiate into all cell types of the adult body, which collectively include human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) [5].
How do organoids help in understanding disease mechanisms?
Organoids can recreate the advanced structure and cellular heterogeneity of their mother organs. Subsequently, organoids are making advancements in medicine by serving as valuable tools for drug screening and disease modeling.
How do organoids help with personalized medical treatments?
Organoids derived from patients accurately mirror the physiology and genetic makeup of the source tissue, offering a reliable platform for evaluating the toxicity of drugs in the preclinical phase. Our sophisticated culture methods facilitate the combination of immune cells and stromal elements in a co-culture system, accurately simulating the tissue’s microenvironment complexity [6].
What are the technical challenges in creating and maintaining organoids?
While in vitro culture systems generally lack a physiological context, there are further difficulties in producing a three-dimensional live mass of tissue suspended in culture fluid. Over time, growing organoids' interiors become more and more covered in necrotic tissue due to hypoxia and lack of perfusion.
How are these ‘mini-organs’ advancing medicine?
Organoids can be used by researchers to simulate genetic illnesses and evaluate therapeutic approaches by utilizing CRISPR-Cas9 and other gene-editing techniques. This represents a huge advancement in the field of personalized medicine.
Organoids are a huge advance in biomedical science that provide previously unheard-of possibilities for simulating illnesses, comprehending human biology, and creating customized therapies. They are crucial instruments for drug testing, regenerative medicine, and customized healthcare because of their capacity to replicate the complexity and performance of actual organs.
Conclusion
Organoids have revolutionized our approach to studying human biology and disease, providing unprecedented insights and novel therapeutic avenues. As this field progresses, the integration of advanced technologies and interdisciplinary collaboration will be crucial in overcoming current limitations. Future research focusing on enhancing organoid complexity and mimicking the in vivo environment more accurately holds great promise. The journey of organoid research is still in its infancy, yet it harbors the potential to transform medicine, offering hope for personalized treatments and deeper understanding of human development. Embracing these advancements will be pivotal in shaping the future of biomedical science.
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Sources:
Yang, Siqi, et al. “Organoids: The current status and biomedical applications.” PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192887/
Barbuzano, Javier “Organoids: A new window into disease, development and discovery” Harvard Stem Cell Institute, https://hsci.harvard.edu/organoids
Yin, Xiaolei, et al. “Stem Cell Organoid Engineering” PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728053/
“Neural Organoids” STEMCELL technologies, https://www.stemcell.com/technical-resources/area-of-interest/organoid-research/neural-organoids/overview.html
Chen, Kevin G., et al. “Pluripotent Stem Cell Platforms for Drug Discovery” Science Direct, https://www.sciencedirect.com/science/article/abs/pii/S1471491418301369
“Toxicology” HUB Organoids, https://www.huborganoids.nl/toxicology/#:~:text=Organoids%20derived%20from%20patients%20accurately,drugs%20in%20the%20preclinical%20phase.