Organoids for Biomedical Research Applications

I woke up to this news that: Scientists Just Solved Organoids' Biggest Problem! I’m happy to share highlights from a new Science paper by Dr. Oscar Abilez, Dr. Huaxiao 'Adam' Yang, Dr. Joseph C. Wu, and colleagues, a leap forward for organoid technology and regenerative medicine! What Did They Do? Stanford researchers have created the first heart and liver organoids with integrated, functional blood vessels. This solves a critical bottleneck: until now, organoids could only grow a few millimeters before their centers died from lack of oxygen and nutrients. With built-in vasculature, these mini-organs can grow larger, mature further, and better mimic real human tissues. How Did They Do It? *The team meticulously optimized a “recipe” of growth factors and signaling molecules, guiding pluripotent stem cells to differentiate into not just heart or liver cells, but also endothelial and smooth muscle cells that self-organize into branching blood vessels. *Their protocol mirrors early embryonic development, allowing the organoids to achieve a cellular complexity similar to a 6.5-week-old human embryonic heart, including beating function! Why Is This Important? *Better Disease Models: Vascularized organoids allow researchers to study early human development and test how drugs impact organ growth and blood vessel formation. *Personalized Medicine: These models can be tailored from patient-derived stem cells, paving the way for individualized drug testing and disease modeling. *Regenerative Therapies: In the future, vascularized cardiac organoids could be implanted to repair damaged heart tissue, offering a more complete cellular environment than current cell therapies Clinical Context As Dr Joseph C. Wu notes, ongoing clinical studies are already injecting lab-grown cardiomyocytes into patients with heart dysfunction. But real heart tissue is much more complex, containing blood vessels, pericytes, fibroblasts, and more. Vascularized organoids could one day provide all these cell types in a single, implantable tissue patch, dramatically improving integration and function. What’s Next? The team aims to: *Grow organoids longer to assess their maturation and size limits *Further refine the recipes to include immune and blood cells *Adapt this vascularization approach to other organs, moving closer to true “mini-organs” for research and therapy A huge CONGRATULATIONS to the entire Stanford team! References: https://lnkd.in/gmYc-cX9 https://lnkd.in/gbntyWgN https://lnkd.in/g-YT5wdU

Our latest paper is out in Nature today! Zonation is a design principle of the human liver. For decades, scientists have known that liver function varies by zone — with diseases like DILI (Drug-Induced Liver Injury) and MASLD often striking specific areas near the central vein. Yet, no human stem cell-derived model has been able to reproduce this complexity — until now. In this study, we report the first human iPSC-derived liver organoids that exhibit controlled zonation, capturing real metabolic gradients across the lobule. 👉 Read the full paper: https://rdcu.be/eh3nX • We restored a functional Gulo gene (defective in humans) to induce an endogenous ascorbate gradient, layered with bilirubin to simulate natural zonation cues. • Zonally primed organoid can fuse to self-assemble and reconstruct all three zones. • Zone-specific functions and toxicities revealed: several drugs target only zone 1 or zone 3 hepatocytes. • Elastic epigenetic regulation uncovered — driven by TET1 (ascorbate) and HIF1A (bilirubin). • Multi-zonal organoid transplantation reduces total liver dysfunction as a promising strategy for regeneration. This project was led by my first US based PhD student, Hasan Al Reza, PhD, who immigrated from Bangladesh to pursue science with passion and resilience. Deep gratitude to the team at Cincinnati Children's for pushing the boundary of human organoid models. #Organoids #LiverZonation #StemCells #GuloGene #AscorbateGradient #RegenerativeMedicine #iPSC #DrugDiscovery #PrecisionMedicine #DiversityInSTEM #NaturePaper #DILI

Liver fibrosis is a complex, progressive liver scarring condition affecting millions globally with very few treatment options. Driven by this unmet need, we have been collaborating with Dr Gary Peltz at Stanford University School of Medicine to explore how our Google DeepMind Google Research AI co-scientist might assist in uncovering novel therapeutic avenues for this challenging disease. Really excited to share comprehensive experimental validation results, led by Yuan Guan, Jakkapong Inchai, Zhuoqing Fang from Dr. Peltz’s lab, demonstrating our co-scientist's efficacy in uncovering promising targets and drug repurposing candidates for this disease. We specifically tasked the AI co-scientist with the challenge: "Propose novel hypotheses about specific epigenetic changes contributing to myofibroblast formation in liver fibrosis and indicate what drugs should we test as new treatments... Novel experiments performed in hepatic organoids are preferred". The AI co-scientist proposed that epigenetic alterations, particularly histone deacetylation and changes in DNA methylation, are crucial in driving fibrosis. It then suggested specific drug classes to test this, including HDAC inhibitors (like Vorinostat), DNMT inhibitors, and Bromodomain (BRD4) inhibitors. In subsequent experiments using a high-throughput micro-human hepatic organoid (microHO) platform pioneered by Dr Peltz’s lab, we found that: 1. Vorinostat (an FDA-approved HDAC inhibitor) and BRD4 inhibitors indeed showed potent anti-fibrotic effects in our human liver organoid models, without causing toxicity at effective concentrations. 2. Further supporting the co-scientist's line of reasoning, Vorinostat was observed to significantly reduce TGFβ-induced chromatin structural changes (by 91%) and also promoted the regeneration of liver parenchymal cells. While the DNMT1 inhibitor suggested by the system did not prove effective, the success with HDAC and BRD4 inhibitors highlights the AI co-scientist's potential to act as a valuable partner for scientists tackling complex diseases. By helping formulate detailed, testable hypotheses rooted in scientific literature, the co-scientist can meaningfully assist in navigating the complexities of disease and rapidly accelerate the path towards new cures. Notably, this work was done with an older version of the system.  We have made considerable progress building on the latest Gemini 2.5 models and look forward to sharing more progress soon. Huge thanks to our incredible collaborators at Stanford and with amazing teammates at Google Research Google DeepMind Google Cloud: Tao Tu, Juro Gottweis Yunhan Xu Keran Rong Artiom Myaskovsky Alexander Daryin Annalisa Pawlosky Kavita Kulkarni Anil Palepu Wei-Hung Weng Alan Karthikesalingam MD PhD Preprint link - https://lnkd.in/eADZ8tJd AI co-scientist blog - https://lnkd.in/gEDeaRfu

3D-bioprinted tumor organoids for personalized pediatric cancer treatment. Researchers created patient-derived tumor models using engineered ECM-mimic hydrogels and high-throughput 3D bioprinting. Organoids from neuroblastoma and sarcoma patients retained tumor features and enabled rapid, individualized drug screening—addressing major barriers in biopsy access and expansion. Gene expression guided hydrogel design, ensuring the models matched each tumor’s unique microenvironment. Wasatch Biolabs supports studies like this with full-length RNA and cDNA sequencing, delivering deeper insights into isoform diversity, fusion transcripts, and tumor-specific expression patterns—critical for validating complex 3D models. Read the full paper here: https://lnkd.in/gA4aZCP2 #PediatricCancer #3DBioprinting #PrecisionMedicine

Excited to share our latest review in Current Opinion in Biomedical Engineering: 👉 “Diversity in a Dish: Leveraging Organoids to Reflect Genetic Ancestry and Sex Differences in Health and Disease” 🔗 https://lnkd.in/eCpAZSBH Together with colleagues from Doppl SA and the University of Cape Town, our team at Cincinnati Children’s explores how stem cell–derived organoid models can help close persistent gaps in biomedical research—by modeling population-level diversity in ancestry and sex from the earliest stages of drug development. This comes at a pivotal moment for the microphysiological systems (MPS) field: 🔹 The FDA Modernization Act 2.0 enables drug developers to use human-based models in place of traditional animal testing 🔹 The NIH has committed to prioritizing funding for non-animal, human-relevant technologies (🔗 https://lnkd.in/eghDFAYZ) 🔹 The FDA recently laid out its roadmap to formally phase in alternatives to animal testing (🔗 https://lnkd.in/eGnw_CzQ) As organoids gain traction for safety, efficacy, and disease modeling, their ability to reflect true human biological variation offers a powerful tool for advancing both precision and equity in medicine. Proud of this global collaboration and what it represents for the future of inclusive, human-relevant science. #Organoids #MPS #iPSC #DrugDiscovery #PersonalizedMedicine #RegulatoryScience #DiversityInResearch #CuSTOM #CincinnatiChildrens

Happy Friday all! Check out this open access Nature Gene Therapy review by Vivienne M. Kaiser & Anai Gonzalez-Cordero, "Organoids – the future of pre-clinical development of AAV gene therapy for CNS disorders." Abstract: Advancements in our understanding of genetic disease and adeno-associated virus has prompted great excitement into the field of AAV-mediated gene therapy, particularly for genetic diseases of the central nervous system, including retinal disorders. Despite significant progress, exemplified by the approval of therapies such as Luxturna® and Zolgensma®, a substantial number of therapies remain in pre-clinical or early clinical stages, with many failing to advance to later phases. Whilst the use of animal models to test safety and delivery route efficacy of AAV treatments is imperative, differences in tissue structure and physiology between humans and animal models has restricted precise disease modelling and gene therapy development for many CNS disorders. Alongside the FDA push for non-animal alternative models, researchers are increasingly turning to human-based models, including stem cell-derived organoids, which can offer a more accurate representation of human cellular microenvironments and niches. As such, this review explores the advantages and limitations of brain and retinal organoids as pre-clinical models of disease, with a primary focus on their utility in identifying novel AAV capsids, cell-specific promoters, and their role in recent pre-clinical AAV gene therapy studies. #drugdiscovery #aav #cns #retina #organoids #scientificresearch

LAB-GROWN NERVE CIRCUIT RECREATES HUMAN PAIN PATHWAY Researchers have recreated the human ascending sensory pathway in a lab dish, using organoids that model the key brain and spinal cord regions responsible for transmitting pain. This breakthrough allows scientists to observe how pain signals travel from peripheral neurons to the brain for the first time outside the body. The model, called an assembloid, responds to pain-inducing stimuli and reflects the effects of genetic mutations known to alter pain perception. This innovation could revolutionize drug discovery for pain relief, particularly for conditions like chronic pain or hypersensitivity. 3 Key Facts: 1. Full Pain Pathway Recreated: Four connected brain and spinal organoids simulate human pain signal transmission. 2. Drug Discovery Platform: The assembloid enables testing of pain-inducing chemicals and potential pain-blocking drugs. 3. Gene-Specific Insights: Mutations in Nav1.7 sodium channels altered wave-like neural activity, mimicking pain disorders. Source: https://lnkd.in/g-sRD84B

🚀 In non-AI news, I am excited to share just published work from our team at the Englander Institute. The research described in this new paper in the journal Cancer Research is a significant step forward in pooled CRISPR screening in patient-derived tumor organoids (PDTOs)—bringing us closer to functional precision medicine. Co-led by Laura Martin, Melissa Davis, and Florencia Madorsky Rowdo, this study demonstrates the power of CRISPR-based functional genomics to uncover new therapeutic opportunities. 🔬 Key Highlights: ✅ One of the first pooled CRISPR screens in patient-derived organoids, overcoming technical challenges in 3D tumor models. ✅ Identified essential kinase dependencies that drive tumor viability, revealing potential therapeutic targets. ✅ Discovered synergy between EGFR and FGFR1 inhibition, opening new avenues for combination therapy. By applying functional genomic screening in 3D patient-derived models, we can move beyond genetic alterations to directly identify druggable vulnerabilities, providing a powerful complement to traditional precision oncology approaches. 📖 Read the full study here: https://lnkd.in/e3MW7Kqh and preprint here: https://lnkd.in/ekTbDrgw Proud of our fantastic team and collaborators—excited to see how these findings advance CRISPR-based functional screening and cancer therapy!

"Patient-derived Tumor Organoids: Generation and Applications in Disease Modeling and Personalized Therapy" A recent review with 108 references and sections on liver, lung, breast, GI, bladder, pancreas, ovarian, head and neck applications. https://lnkd.in/gfizPYcj

Scientists Create Mini-Brains That Resemble a 40-Day-Old Fetus A Major Leap in Brain Research Researchers at Johns Hopkins University have successfully fused different human organoids to create “mini-brains” that contain approximately 80% of the cell types found in a 40-day-old fetal brain. This breakthrough moves scientists closer than ever to replicating early human brain development in the lab, providing a powerful tool for studying neurological diseases and brain disorders. Bridging the Gap Between Mice and Humans Mini-brains—also known as multi-region brain organoids—are particularly valuable for studying conditions that do not manifest clearly in animal models, such as autism, schizophrenia, and neurodevelopmental disorders. According to lead researcher Annie Kathuria, these lab-grown structures are “a little better than a mouse, a little less than a human”, making them a crucial middle ground for neuroscience research. The ability to replicate human-specific brain development is essential for fields like disease modeling, drug testing, and toxicology studies. By ensuring these organoids closely resemble human fetal brains, scientists can now investigate how environmental factors, genetics, and medications influence early neural development in ways that were previously impossible. Why This Matters for Brain Science • Improved Disease Research – Mini-brains allow scientists to model neurological disorders in human-like systems, leading to better diagnostic and treatment strategies. • Ethical and Practical Advantages – These lab-grown structures offer a way to study human brain development without using fetal tissue. • Toxicology and Environmental Studies – Researchers can now test how drugs, pollutants, and toxins impact the developing brain with greater accuracy. The Future of Lab-Grown Brain Models While these mini-brains are still simplified versions of real human brains, their ability to mimic fetal development represents a major step forward. As organoid technology advances, scientists hope to refine these models further, potentially unlocking new treatments for neurodevelopmental disorders and improving our understanding of the human brain’s earliest stages.