Organoids: The Future of Lab-grown Human Tissues
- Admin
- Mar 31
- 5 min read
Since the early 2000s, organoids, 3D tissue structures mimicking the structure and function of human organs, have emerged as one of the most promising innovations in biomedical research. With the complex architecture and functionality of their full-scale, natural counterparts, organoids provide scientists with the unique opportunity to study our tissues’ development, function and disease progression. As scientists continue to refine methods for growing and researching organoids, these lab-grown tissues have potential for groundbreaking impact in fields from disease modeling and drug testing to personalized medicine.
The history of organoids
In 1907, Henry Van Peters Wilson at University of North Carolina announced a breakthrough discovery in the Journal of Experimental Zoology: the resonrtcution of silicate sponges into functional creatures after the individual cells had been dissociated from one another by fragmentation and straining through a fine mesh sieve. Little did he know that he was paving the way for a new application of bioengineering - the development of organoids.
Over the years, many researchers conducted similar experiments with amphibian pronephros and chick embryos, deepening our understanding of the dissociation and differentiation process. Then, in 1981, pluripotent stem cells (PSCs) were successfully isolated from mouse embryos, followed by embryonic stem cells from human blastocysts in 1998.
By 2006, cell culture conditions had improved considerably and almost simulated the in vivo microenvironment. This led to the discovery of induced PSCs (iPSCs), a major breakthrough in stem cell research.
In 2009, researchers finally managed to prove that Lgr5-expressing adult intestinal stem cells could form self-organizing intestinal organoids in Matrigel capable of differentiating into natural crypt-villus structures. This was the first time a 3D organoid culture had been established from a single adult cell, opening doors for further research on various systems like mesendoderm-derived (like the stomach, liver, pancreas, lung, and kidney) and neuroectoderm-derived tissues (such as the brain and retina).
How do you make organoids?
Organoids, also known as “mini-organs”, are 3D miniature versions of organs or tissues, produced through the self-organization of stem cells in vitro. They are usually grown from embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), neonatal stem cells or adult stem cells (ASCs), which can self-organize and recapitulate into cell masses with the same morphology and purpose as in vivo tissues, such as the brain, liver, intestine and kidney. As such, organoid engineering is similar to organism development from a zygote to adult stage, undergoing culture-controlled differentiation and self-organization.
Firstly, stem cells are isolated and cultured in an environment mimicking human body conditions, created through bioengineering organoid systems. A scaffold as a biological or synthetic hydrogel is usually use to mimic the properties of extra cellular matrix (ECM). For example, growth factors manipulating signaling pathways, biochemical cues and Matrigel can be used to assist their self-organization and differentiation. Over time, they form layered, 3D structures recapitulating many features of real tissues. This self-organization is one of the most remarkable aspects of the capability of cells to know how to form functional tissue given the suitable conditions.
Applications of organoid technology
The potential applications of organoids in research and medicine are vast, making them a focus of many studies.
One of the most significant uses is disease modeling. While traditional models like 2D cell structures or animal models cannot fully simulate cell-cell and cell-extracellular interactions as well as the natural structures of humans and tissues, organoids can provide a more realistic representation of tissue complexity. Not only can they be used to study infections by viruses, bacteria and parasites like SARS-CoV-2, they also allow for the study of genetic mutations on organ development in a way not feasible in vivo. Applications include studying pathogenic mechanisms, the development of neural circuits in brain function, investigating factors in inflammation and aging, and testing therapeutic techniques for diseases with unknown etiology like type 1 diabetes. This can lead to significant advances in research and treatment on difficult conditions like cancer, neurodegenerative and infectious diseases.
Furthermore, they are also useful in drug and treatment testing. Pharmaceutical companies face high attrition rates in drug development because traditional testing models don’t always predict human responses regularly. Organoids can provide insights into mechanisms of drug actions and efficacy and toxicity without relying on animal or human testing.
Additionally, personalized medicine stands to benefit greatly. Using patient-derived organoids (PDO), which can recapitulate unique aspects of patient physiology and disease phenotypes like genetic profiles and drug sensitivities, they are suitable to capture the clinical heterogeneity of diseases like cancers for research purposes. For instance, organoids have been used to discover links between genetic mutations and sensitivities to certain therapies, from which patient response can be predicted.
In regenerative medicine such as organ transplantation, normally hindered by sample availability and ethical issues, organoids offer an alternative pathway. Stem-cell derived 3D-organoid cultures can improve reproducibility and genetic correction for more personalized treatment. Researchers are investigating whether organoids can be used to replace damaged tissues or organs, bypassing the need for donor organs. Although the field is still in its infancy, one day, organoids could be used to repair heart tissue after myocardial infarctions, or restore function in degenerative diseases by replacing damaged neurons or liver cells. These advances could offer new hope to patients with chronic organ failure.
Challenges of organoid technology
Despite a promising future, their utility is limited by a lack of high-fidelity cell types, limited maturation and atypical physiology. Bioengineering tools are not yet advanced enough to organize stem cells and their niche. Additionally, study of highly specified cell types, functional circuit formation and activity and interactions between CNS-resident neuronal and nonneuronal types is limited due to its complexity. Differences in genetic background and variability in biobank samples can also cause misinterpretation of phenotypes.
Regarding ethics, consent and privacy issues are paramount when culturing patient cells for organoid creation and research as it contains sensitive genetic information. Moreover, self-organisation of organoids raises further questions, like: could organoids used to model the human brain gain consciousness or sentience? Although current research indicates that they don’t have complex neural networks required, advancements in the field are rapid, necessitating ongoing ethical scrutiny.
Under a regulatory lens, clinical applications of organoid research also present a barrier. Traditional models for assessing drug safety and efficacy are not entirely applicable due to organoids’ unique properties.
Thus, guidelines must be established together with scientists and industry stakeholders to safeguard public health.
Article prepared by: Serene Kong, MBIOS R&D Associate 24/25
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