What Is: Organoid

Organoids: The Science and Ethics of Mini-Organs
Image Credit: Scientific Frontline / AI generated

The "At a Glance" Summary

• Defining the Architecture: Unlike traditional cell cultures, organoids are 3D structures grown from pluripotent stem cells (iPSCs) or adult stem cells. They rely on the cells' intrinsic ability to self-organize, creating complex structures that mimic the lineage and spatial arrangement of an in vivo organ.
• The "Avatar" in the Lab: Organoids allow for Personalized Medicine. By growing an organoid from a specific patient's cells, researchers can test drug responses on a "digital twin" of that patient’s tumor or tissue, eliminating the guesswork of trial-and-error prescriptions.
• Bridge to Clinical Trials: Organoids serve as a critical bridge between the Petri dish and human clinical trials, potentially reducing the failure rate of new drugs and decreasing the reliance on animal testing models which often fail to predict human reactions.
• The Ethical Frontier: As cerebral organoids (mini-brains) become more complex, exhibiting brain waves similar to preterm infants, science faces a profound question: At what point does biological complexity become sentience?

Restoring the healthy form of a protein could revive blood vessel growth in premature infants’ lungs

A blood vessel organoid.
Video Credit: Yunpei Zhang and Enbo Zhu, Mingxia Gu Lab

A UCLA-led research team has discovered a molecular switch that determines whether tiny blood vessels in premature infants’ lungs can regenerate after injury. A failure of this repair process is a hallmark of bronchopulmonary dysplasia, or BPD, a serious lung disease that affects babies born very early. It arises from a combination of premature birth, inflammation or infection, and exposure to the high levels of oxygen and breathing support that are necessary to keep these infants alive during a critical period of lung development.

The researchers found that in BPD, the blood vessel cells in the lungs begin producing a shortened, nonfunctional isoform — a version of a protein — called NTRK2, which has been extensively studied in the nervous system but not in the pulmonary vasculature. When this shortened isoform dominates, the lung cannot rebuild the delicate network of tiny blood vessels needed for healthy breathing.

The Quest for the Synthetic Synapse

Spike Timing" difference (Biology vs. Silicon)
Image Credit: Scientific Frontline

The modern AI revolution is built on a paradox: it is incredibly smart, but thermodynamically reckless. A large language model requires megawatts of power to function, whereas the human brain—which allows you to drive a car, debate philosophy, and regulate a heartbeat simultaneously—runs on roughly 20 watts, the equivalent of a dim lightbulb.

To close this gap, science is moving away from the "Von Neumann" architecture (where memory and processing are separate) toward Neuromorphic Computing—chips that mimic the physical structure of the brain. This report analyzes how close we are to building a "synthetic synapse."

Reproduced human neural circuits show the crucial role of the thalamus in shaping the cortical circuit

Assembloid [3D fluorescent staining] Axons in the thalamus (pink) extended toward the cortex, while those in the cortex (green) extended toward the thalamus at 14 days post-fusion.
Image Credit: Fumitaka Osakada

A Japanese research team has successfully reproduced the human neural circuit in vitro using multi-region miniature organs known as assembloids, which are derived from induced pluripotent stem (iPS) cells. With this circuit, the team demonstrated that the thalamus plays a crucial role in shaping cell type-specific neural circuits in the human cerebral cortex.

These findings were published in the journal Proceedings of the National Academy of Sciences of the United States of America.

Our brain’s cerebral cortex contains various types of neurons, and effective communication among these neurons and other brain regions is crucial for activating functions like perception and cognition.

Patients with neurodevelopmental disorders, such as autism spectrum disorder (ASD), exhibit disruptions in the structure and function of neural circuits in the cerebral cortex. Therefore, understanding the principles of these circuits is essential to uncovering the causes of these disorders and developing new medications.

Researchers build bone marrow model entirely from human cells

Scanning electron microscopy image of the engineered 3D bone marrow tissue colonized with human blood cells (red).
Image Credit: Andrés García-García, University of Basel, Department of Biomedicine

Our body’s “blood factory” consists of specialized tissue made up of bone cells, blood vessels, nerves and other cell types. Now, researchers have succeeded for the first time in recreating this cellular complexity in the laboratory using only human cells. The novel system could reduce the need for animal experiments for many applications.

The bone marrow usually works quietly in the background. It only comes into focus when something goes wrong, such as in blood cancers. In these cases, understanding exactly how blood production in our body works, and how this process fails, becomes critical. 

Typically, bone marrow research relies heavily on animal models and oversimplified cell cultures in the laboratory. Now, researchers from the Department of Biomedicine at the University of Basel and University Hospital Basel have developed a realistic model of bone marrow engineered entirely from human cells. This model may become a valuable tool not only for blood cancer research, but also for drug testing and potentially for personalized therapies, as reported by a team of researchers led by Professor Ivan Martin and Dr Andrés García-García in the journal Cell Stem Cell. 

A cellular protein, FGD3, boosts breast cancer chemotherapy, immunotherapy

The research team included, front row, from left: graduate student Junyao Zhu, biochemistry professor David Shapiro, and senior researcher Chengiian Mao; back row, from left: graduate students Abigail Spaulding, Xinyi Dai and Qianjin Jiang.
Photo Credit: Fred Zwicky

A naturally occurring protein that tends to be expressed at higher levels in breast cancer cells boosts the effectiveness of some anticancer agents, including doxorubicin, one of the most widely used chemotherapies, and a preclinical drug known as ErSO, researchers report. The protein, FGD3, contributes to the rupture of cancer cells disrupted by these drugs, boosting their effectiveness and enhancing anticancer immunotherapies.

The new findings were the happy result of experiments involving ErSO, an experimental drug that killed 95-100% of estrogen-receptor-positive breast cancer cells in a mouse model of the disease. ErSO upregulates a cellular pathway that normally protects cancer cells from stress, said University of Illinois Urbana-Champaign biochemistry professor David Shapiro, who led the new work with Illinois graduate student Junyao Zhu. But when that protective pathway is ramped up, the system goes awry.

Did Lead Limit Brain and Language Development in Neanderthals and Other Extinct Hominids?

UC San Diego researchers have found high levels of lead in the teeth of both Neanderthals (left) and modern humans (right). However, a gene mutation may have protected modern human brains, allowing language to flourish.
Photo Credit: Kyle Dykes/UC San Diego Health Sciences

Ancient human relatives were exposed to lead up to two million years ago, according to a new study. However, a gene mutation may have protected modern human brains, allowing language to flourish.

What set the modern human brain apart from our now extinct relatives like Neanderthals? A new study by University of California San Diego School of Medicine and an international team of researchers reveals that ancient hominids — including early humans and great apes — were exposed to lead earlier than previously thought, up to two million years before modern humans began mining the metal. This exposure may have shaped the evolution of hominid brains, limiting language and social development in all but modern humans due to a protective genetic variant that only we carry. The study was published in Science Advances.

The researchers analyzed fossilized teeth from 51 hominids across Africa, Asia and Europe, including modern and archaic humans such as Neanderthals, ancient human ancestors like Australopithecus africanus, and extinct great apes such as Gigantopithecus blacki.

Brain inflammation treatment could be ally in fight against dementia

Samira Aghlara-Fotovat
Photo Credit: Jeff Fitlow/Rice University

Scientists from Rice University and Houston Methodist have developed a new way to reduce inflammation in the brain, a discovery that could help fight diseases such as Alzheimer’s and Parkinson’s.

The team created “AstroCapsules,” small hydrogel capsules that enclose human astrocytes ⎯ star-shaped brain cells that support healthy nervous system function. Inside the capsules, the cells were engineered to release interleukin-1 receptor antagonist, an anti-inflammatory protein. Tests in human brain organoids and mouse models showed the treatment lowered neuroinflammation and resisted immune rejection.

Rice bioengineer Omid Veiseh, whose lab studies how to design biomaterials that work with the immune system, is co-corresponding author on the paper published in Biomaterials.

“Encapsulating cells in a way that shields them from immune attack has been a central challenge in the field,” said Veiseh, professor of bioengineering at Rice, Cancer Prevention and Research Institute of Texas Scholar and director of the Rice Biotech Launch Pad. “In our lab, we have been working on biomaterials for many years, and this project was an opportunity to draw from that experience to address the uniquely complex immune environment of the brain. Our hope is that this work will help move cell therapies closer to becoming real treatment options for patients with neurodegenerative disease.”

Scientists discover potential treatment approaches for polycystic kidney disease

cientists would like to know how cysts form in polycystic kidney disease (PKD). Here, they compared two 3-D mini-kidney models. On the left, a model shows a mini kidney with a gene mutation that causes cysts to form. On the right, researchers used gene editing to correct a gene mutation, preventing the development of cysts.
Image Credit: Vishy, et al., Cell Stem Cell 2024

Researchers have shown that dangerous cysts, which form over time in polycystic kidney disease (PKD), can be prevented by a single normal copy of a defective gene. This means the potential exists that scientists could one day tailor a gene therapy to treat the disease. They also discovered that a type of drug, known as a glycoside, can sidestep the effects of the defective gene in PKD. The discoveries could set the stage for new therapeutic approaches to treating PKD, which affects millions worldwide. The study, partially funded by the National Institutes of Health (NIH), is published in Cell Stem Cell.

Scientists used gene editing and 3-D human cell models known as organoids to study the genetics of PKD, which is a life-threatening, inherited kidney disorder in which a gene defect causes microscopic tubes in the kidneys to expand like water balloons, forming cysts over decades. The cysts can crowd out healthy tissue, leading to kidney function problems and kidney failure. Most people with PKD are born with one healthy gene copy and one defective gene copy in their cells.

“Human PKD has been so difficult to study because cysts take years and decades to form,” said senior study author Benjamin Freedman, Ph.D., at the University of Washington, Seattle. “This new platform finally gives us a model to study the genetics of the disease and hopefully start to provide answers to the millions affected by this disease.”

Not unique to humans but uniquely human: researchers identify factor involved in brain expansion in humans

A microscopy image of a human brain organoid.
Image Credit: © Janine Hoffmann

What makes us human? According to neurobiologists it is our neocortex. This outer layer of the brain is rich in neurons and lets us do abstract thinking, create art, and speak complex languages. An international team led by Dr. Mareike Albert at the Center for Regenerative Therapies Dresden (CRTD) of TUD Dresden University of Technology has identified a new factor that might have contributed to neocortex expansion in humans. The results were published in the EMBO Journal.

The neocortex is the characteristic folded outer layer of the brain that resembles a walnut. It is responsible for higher cognitive functions such as abstract thinking, art, and language. “The neocortex is the most recently evolved part of the brain,” says Dr. Mareike Albert, research group leader at the CRTD. “All mammals have a neocortex, but it varies in size and complexity. Human and primate neocortices have folds while, for example, mice have a completely smooth neocortex, without any creases.”

The folds characteristic of the human brain increases the surface area of the neocortex. The human neocortex has a greater number of neurons that support complex cognitive functions.

The molecular mechanisms driving neocortex evolution are still largely unknown. “Which genes are responsible for inter-species differences in neocortex size? What factors have contributed to brain expansion in humans? Answering these questions is crucial to understanding human brain development and potentially addressing mental health disorders,” explains Dr. Albert.

Human stem cells coaxed to mimic the very early central nervous system

Jianping Fu, Ph.D., Professor of Mechanical Engineering at the University of Michigan and the corresponding author of the paper being published at Nature discusses his team’s work in their lab with Jeyoon Bok, Ph.D. candidate at the Department of Mechanical Engineering.
Photo Credit: Marcin Szczepanski, Michigan Engineering

The first stem cell culture method that produces a full model of the early stages of the human central nervous system has been developed by a team of engineers and biologists at the University of Michigan, the Weizmann Institute of Science, and the University of Pennsylvania.

“Models like this will open doors for fundamental research to understand early development of the human central nervous system and how it could go wrong in different disorders,” said Jianping Fu, U-M professor of mechanical engineering and corresponding author of the study in Nature.

The system is an example of a 3D human organoid—stem cell cultures that reflect key structural and functional properties of human organ systems but are partial or otherwise imperfect copies.

“We try to understand not only the basic biology of human brain development, but also diseases—why we have brain-related diseases, their pathology, and how we can come up with effective strategies to treat them,” said Guo-Li Ming, who along with Hongjun Song, both Perelman Professors of Neuroscience at UPenn and co-authors of the study, developed protocols for growing and guiding the cells and characterized the structural and cellular characteristics of the model.

New treatment for deadly uterine cancer

left to right, Dr Asmerom Sengal, Professor Pamela Pollock.
Photo Credit: Courtesy of Queensland University of Technology

QUT scientists have discovered a promising new therapy for a deadly type of endometrial cancer that has a poor prognosis if the cancer spreads or returns after initial treatment, a plight that affects 15-20 per cent of endometrial cancer patients.

• Testing of new drug inhibited uterine tumor cell growth in lab and mice models

• The drug blocks the receptor of the growth factor in tumors that is associated with a low survival rate

• The inhibitor also reduced the tumors blood vessel formation

Dr Asmerom Sengal and Associate Professor Pamela Pollock from QUT’s School of Biomedical Sciences, published their research in Nature Precision Oncology with a recommendation that the strength of their findings indicated they should proceed to patient trials.

Dr Asmerom said endometrial cancer confined within the uterus could be cured with surgery however, if it had spread to the abdomen and other organs patients had limited treatment options.

“Previously, we found women with endometrial cancer who have an incorrect growth factor receptor called fibroblast growth factor receptor 2c (FGFR2c) on the tumor cell surface have a poor survival rate,” Dr Asmerom said.

Cancer research: Metabolite drives tumor development

Tumor organoids (green/blue) are used as a model to study the metabolic changes in liver cell cancer.
 Image Credit: Dr. Sandro Nuciforo, Department of Biomedicine, University of Basel

Cancer cells are chameleons. They completely change their metabolism to grow continuously. University of Basel scientists have discovered that high levels of the amino acid arginine drive metabolic reprogramming to promote tumor growth. This study suggests new avenues to improve liver cancer treatment.

The liver is a vital organ with many important functions in the body. It metabolizes nutrients, stores energy, regulates the blood sugar level and plays a crucial role in detoxifying and removing harmful components and drugs. Liver cancer is one of the world’s most lethal types of cancer. Conditions that cause liver cancer include obesity, excessive alcohol consumption and hepatitis C infection. Early diagnosis and appropriate therapeutic strategies are crucial for improving treatments in liver cancer.

Cancer as a metabolic disease

In the past decade, scientists have made much progress in understanding the multiple facets of cancer. Historically, it has long been viewed as a disorder in cell proliferation. However, there is growing evidence that cancer is a metabolic disease. In other words, cancer arises when cells rewire their metabolism to allow uncontrolled cell proliferation. How do cells change their metabolism and how does this change in turn lead to tumorigenicity? With their new study in “Cell”, researchers led by Professor Michael N. Hall at the Biozentrum, University of Basel, have discovered a key driver of metabolic rewiring in liver cancer cells.

Fine-tuning 3D lab-grown mini tumors to help predict how patients respond to cancer therapies

The improved process allows researchers to use an advanced imaging method to study and analyze individual organoids in great detail.
Image Credit: Soragni Lab.

Scientists from the UCLA Jonsson Comprehensive Cancer Center have developed a new method to bio-print miniature tumor organoids that are designed to mimic the function and architecture of real tumors. The improved process allows researchers to use an advanced imaging method to study and analyze individual organoids in great detail, which can help researchers identify personalized treatments for people with rare or hard-to-treat cancers.

The method is described in the journal Nature Communications.

“Tumor organoids have become fundamental tools to investigate tumor biology and highlight drug sensitivities of individual patients,” said Alice Soragni, PhD, an assistant professor in the department of Orthopedic Surgery at the David Geffen School of Medicine at UCLA and member of the UCLA Jonsson Comprehensive Cancer Center. “However, we still need better ways to anticipate if resistance could be arising in a small population of cells, which we may not detect using conventional screening approaches. This is truly important, particularly as organoid-based drug predictions are starting to be leveraged clinically.”

Brain research with organoids

Section of an electroporated brain organoid of a common marmoset. Green: electroporated cells that glow green due to the green fluorescent protein; magenta: neurons; gray: nuclei.
Photo Credit: Lidiia Tynianskaia

Scientists at the German Primate Center develop effective method to genetically modify brain organoids

Primates are among the most intelligent creatures with distinct cognitive abilities. Their brains are relatively large in relation to their body stature and have a complex structure. However, how the brain has developed over the course of evolution and which genes are responsible for the high cognitive abilities is still largely unclear. The better our understanding of the role of genes in brain development, the more likely it will be that we will be able to develop treatments for serious brain diseases. 

Researchers are approaching these questions by knocking out or activating individual genes and thus drawing conclusions about their role in brain development. To avoid animal experiments as far as possible, brain organoids are used as an alternative. These three-dimensional cell structures, which are only a few millimeters in size, reflect different stages of brain development and can be genetically modified. However, such modifications are usually very complex, lengthy and costly. Researchers at the German Primate Center (DPZ) – Leibniz Institute for Primate Research in Göttingen have now succeeded in genetically manipulating brain organoids quickly and effectively. 

A new at­las il­lus­trates how the hu­man ret­ina is de­vel­op­ing.

De­tail of a cross-​section of a ret­inal or­ganoid. Dif­fer­ent tis­sue struc­tures are made vis­ible with dif­fer­ent colors.
Pho­to­ Credit: Wahle et al. Nature Bi­o­tech­no­logy 2023

What cell types are found in which hu­man tis­sue, and where? Which genes are act­ive in the in­di­vidual cells, and which pro­teins are found there? An­swers to these ques­tions and more are to be provided by a specialized at­las – in par­tic­u­lar how the dif­fer­ent tis­sues form dur­ing em­bryonic de­vel­op­ment and what causes dis­eases. In cre­at­ing this at­las, re­search­ers aim to map not only tis­sue dir­ectly isol­ated from hu­mans, but also struc­tures called or­ganoids. These are three-​dimensional clumps of tis­sue that are cul­tiv­ated in the labor­at­ory and de­velop in a way sim­ilar to hu­man or­gans, but on a small scale.

“The ad­vant­age of or­ganoids is that we can in­ter­vene in their de­vel­op­ment and test act­ive sub­stances on them, which al­lows us to learn more about healthy tis­sue as well as dis­eases,” ex­plains Bar­bara Treut­lein, Pro­fessor of Quant­it­at­ive De­vel­op­mental Bio­logy at the De­part­ment of Biosys­tems Sci­ence and En­gin­eer­ing at ETH Zurich in Basel.

To help pro­duce such an at­las, Treut­lein, to­gether with re­search­ers from the Uni­ver­sit­ies of Zurich and Basel, has now de­veloped an ap­proach to gather and com­pile a great deal of in­form­a­tion about or­ganoids and their de­vel­op­ment. The re­search team ap­plied this ap­proach to the or­ganoids of the hu­man ret­ina, which they de­rived from stem cells.

This killer protein causes pancreatic cancer

Mouse pancreas cells with high levels of the protein SRSF1; CSHL Professor Adrian Krainer found that mice with high levels of SRFS1 tend to exhibit intraepithelial neoplasia—a known precursor to the most common form of pancreatic cancer.
Image Credit: Cold Spring Harbor Laboratory

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. It’s also one of the deadliest. More than 90% of PDAC patients die within five years of diagnosis. Usually, by the time the cancer is identified, it has already spread.

“PDAC is often found too late for treatments like chemotherapy and surgery to be very effective,” Cold Spring Harbor Laboratory (CSHL) Professor Adrian Krainer says. “But if we can clearly understand the underlying genetic mechanisms of PDAC, this might lead to earlier diagnoses and new types of therapies.”

Krainer and CSHL Postdoc Ledong Wan partnered with CSHL Professor David Tuveson to explore the role of a genetic process called RNA splicing in pancreatic cancer. RNA splicing helps DNA deliver instructions to cells for protein production. The team zeroed in on a splicing-regulator protein called SRSF1. They found that high levels of SRSF1 cause inflammation, or pancreatitis. This jumpstarts PDAC tumor development.

Cell mapping and ‘mini placentas’ give new insights into human pregnancy

Cells of the placenta 
Image Credit: Kenny Roberts, Wellcome Sanger Institute

Researchers from the University of Cambridge, the Wellcome Sanger Institute, the Friedrich Miescher Institute for Biomedical Research (FMI), Switzerland, EMBL’s European Bioinformatics Institute (EMBL-EBI), and collaborators, have created an in-depth picture of how the placenta develops and communicates with the uterus.

The study, published today in the journal Nature, is part of the Human Cell Atlas initiative to map every cell type in the human body. It informs and enables the development of experimental models of the human placenta.

"For the first time, we have been able to draw the full picture of how the placenta develops and describe in detail the cells involved in each of the crucial steps. This new level of insight can help us improve laboratory models to continue investigating pregnancy disorders, which cause illness and death worldwide,” said Anna Arutyunyan, co-first author at the University of Cambridge and Wellcome Sanger Institute.

The placenta is a temporary organ built by the fetus that facilitates vital functions such as fetal nutrition, oxygen and gas exchange, and protects against infections. The formation and embedding of the placenta into the uterus, known as placentation, is crucial for a successful pregnancy.

UCLA-led study uses base editing to correct mutation that causes rare immune deficiency

Image Credit: Sangharsh Lohakare

A new UCLA-led study suggests that advanced genome editing technology could be used as a one-time treatment for the rare and deadly genetic disease CD3 delta severe combined immunodeficiency.

The condition, also known as CD3 delta SCID, is caused by a mutation in the CD3D gene, which prevents the production of the CD3 delta protein that is needed for the normal development of T cells from blood stem cells.

Without T cells, babies born with CD3 delta SCID are unable to fight off infections and, if untreated, often die within the first two years of life. Currently, bone marrow transplant is the only available treatment, but the procedure carries significant risks.

In a study published in Cell, the researchers showed that a new genome editing technique called base editing can correct the mutation that causes CD3 delta SCID in blood stem cells and restore their ability to produce T cells.

The potential therapy is the result of a collaboration between the laboratories of Dr. Donald Kohn and Dr. Gay Crooks, both members of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and senior authors of the study.

Scientists use materials to make stem cells behave like human embryos

Stem cells confined in a circular shape on a soft gel display characteristic of embryonic development.
Photo Credit: University of New South Wales

A serendipitous discovery in the lab has the potential to revolutionize embryo models and targeted drug therapies.

Materials scientists at UNSW Sydney have shown that human pluripotent stem cells in a lab can initiate a process resembling the gastrulation phase – where cells begin differentiating into new cell types – much earlier than occurs in mother nature.

For an embryo developing in the womb, gastrulation occurs at day 14. But in a lab at UNSW’s Kensington campus, Scientia Associate Professor Kris Kilian oversaw an experiment where a gastrulation-like event was triggered within two days of culturing human stem cells in a unique biomaterial that, as it turned out, set the conditions to mimic this stage of embryo development.

“Gastrulation is the key step that leads to the human body plan,” says A/Prof. Kilian.

“It is the start of the process where a simple sheet of cells transforms to make up all the tissues of the body – nerves, cardiovascular and blood tissue and structural tissue like muscle and bone. But we haven’t really been able to study the process in humans because you can’t study this in the lab without taking developing embryonic tissue.