Organoid Research Expands at Cincinnati Children’s
Post Date: May 2, 2025 | Publish Date:
Stem Cell and Organoid Medicine
Research Annual Report 2024
Cincinnati Children’s has been a leader in organoid research since 2010 when Jim Wells, PhD, and colleagues introduced the field to the first functional intestinal organoid grown from induced pluripotent stem cells (iPSCs). Since then our Center for Stem Cell & Organoid Medicine (CuSTOM) has grown and evolved. Now this work involves 37 labs within 16 research divisions, where experts apply organoid and stem cell technologies to a wide range of basic disease research, drug discovery, and tissue engineering projects.
Recent work includes producing specialized brain, heart and lung stem cell lines and organoid models to shed light directly upon the mechanisms of human diseases. Looking ahead, Michael Helmrath, MD, and colleagues are leading an effort to prepare advanced intestine organoids for use in human clinical trials.
Here are some of our key organoid and stem cell advances from fiscal 2024:
Advancing Brain Science Via Human Blood-Brain Barrier Assembloids
In a groundbreaking advance, researchers here have created human brain “assembloids” that for the first time mimic the complex structure and function of the blood-brain barrier (BBB).
These findings, published in Cell Stem Cell, promise to accelerate research and treatment development for a wide range of brain disorders, including stroke, cerebral vascular disorders, brain cancer, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and other neurodegenerative conditions.
“Lack of an authentic human BBB model has been a major hurdle in studying neurological diseases,” says lead corresponding author Ziyuan Guo, PhD. “Our breakthrough involves the generation of human BBB organoids from human pluripotent stem cells, mimicking human neurovascular development to produce a faithful representation of the barrier in growing, functioning brain tissue. This is an important advance because animal models we currently use in research do not accurately reflect human brain development and BBB functionality.”
Brain Organoids Power New Wave of Computer Science Innovation
Another line of brain organoids developed at Cincinnati Children’s is powering a new wave of innovation in computer science.
Experts at Indiana University published a study in Nature Electronics that reported success at developing “Brainoware” that connects brain organoid tissue to a silicon computer chip. The team trained the tiny biocomputer to recognize different human speakers with surprising accuracy.
The news flashed like lightning through the worlds of organoid medicine and computer technology with a surge of articles appearing in outlets including Popular Science, MIT Technology Review, GEN and the Daily Mail Online.
The new biocomputing chip was built using brain organoid tissues developed by Jason Tchieu, PhD, and Mingxia Gu, MD, PhD, both with the Center for Stem Cell & Organoid Medicine (CuSTOM) at Cincinnati Children’s.
First the Small Intestine, Now the Colon Has an Organoid with an Immune System
Building on a 2023 success with small intestine organoids, scientists at Cincinnati Children’s and the Medical University of South Carolina have co-created a colon organoid with an integrated immune system.
The study, published in Cell Stem Cell, was led by first and corresponding author Jorge Munera, PhD, of the MUSC Hollings Cancer Center; co-first author Daniel Kechele, PhD, Division of Developmental Biology at Cincinnati Children’s; and co-corresponding author James Wells, PhD, chief scientific officer for CuSTOM.
The co-authors predict the advanced tissues will accelerate development of personalized treatments for colon-related cancers, inflammatory bowel disease (IBD) and other conditions.
Engineered Organoids Might Serve as Bridge to Liver Transplantation in Severe Jaundice
For a small number of newborns with jaundice, sunlight therapy isn’t enough to prompt their livers to produce enough bilirubin. For these children, receiving a liver transplant has been their main hope for living into adulthood.
Now, the emerging field of organoid medicine suggests a new approach may improve survival chances.
In a series of human organoid and rodent model experiments, a research team led by first author Hasan Al Reza, PhD, and senior author Takanori Takebe, MD, PhD, reports that human liver organoids can be augmented to improve how they filter out bilirubin. Findings were published in Stem Cell Reports.
“It now appears possible for liver organoids to support liver function without necessarily growing a full-sized replacement organ,” Takebe says.
Collaboration to Develop Liver Organoids for Drug Toxicity Screening
In February 2024, the CuSTOM Accelerator Lab at Cincinnati Children’s announced it will lead a multi-year collaborative project as part of the Danaher Corporation’s “Beacons” program to further develop human liver organoid technology as a tool for preclinical testing of prospective new medications to reduce the risk of drug-induced liver injury during clinical trials.
“In addition to Caucasians, our new drug toxicity screening platform will incorporate cells from donors representing diverse ethnic backgrounds, including Asians and African Americans,” says Magdalena Kasendra, PhD, director of research and development at CuSTOM. “This will help address the longstanding underrepresentation of these communities in clinical trials and preclinical research.”
Human Vascular Organoids Reveal Clues for a Potential COVID Treatment
In another specialized use of organoid technology, corresponding author Takanori Takebe, MD, PhD. worked with a team of colleagues in Japan to use vascular organoids to make a significant discovery in the race to develop effective COVID treatments. Their findings were published in the journal Cell Stem Cell.
“We developed a human vascular organoid model that accurately mimics the damage caused by SARS-CoV-2,” says Takebe. “After conducting many proteomic, genetic and other studies, we determined that the severe vascular damage and thrombosis associated with COVID-19 can be mitigated by a long-acting monoclonal antibody that targets the complement amplification cycle regulated by factor D (CFD).”
Next steps include further testing involving “humanized” animal models to accurately assess the impact of a clinical-grade CFD targeted antibody.
Organoids Boost Microbiota Research
A far-reaching study published in the journal Immunity reveals a novel way to control allergic immune responses by adjusting how our intestines produce tuft cells, a lesser-understood element of our immune system that helps combat parasitic worm infections.
The project, led by Theresa Alenghat, VMD, PhD, and Emily Eshleman, PhD, both from the Division of Immunobiology, involved a combination of mouse models and using human intestinal organoids as a living test platform to document how commensal gut microbiota interact with tuft cells to affect the intensity of type 2 immune reactions that occur with chronic inflammatory conditions such as allergy and asthma.
With key elements involved in this developmental pathway identified, these findings open doors to designing new diet and microbiome approaches for preventing (or promoting) type 2 inflammation, Alenghat says.
Novel Approach Emerging for Rescuing Limbs at Risk
Across the United States, about 2 million people are living with an amputation and another 185,000 amputations occur every year, according to the Amputee Coalition, a Washington, DC-based support group. About 54% of these lost limbs were caused by vascular disease, including diabetes and peripheral arterial disease (PAD).
Now, experts at Cincinnati Children’s, in collaboration with colleagues from Kanazawa University in Japan, have developed a way to use organoids to prompt blood vessel growth and potentially prevent ischemia-induced amputations. The study, published in Cell Reports Medicine, was led by first author Oto Inoue, MD, PhD, a cardiologist from Japan and a research fellow with Cincinnati Children’s, and Juan Sanchez-Gurmaches, PhD, Division of Endocrinology.
In addition to data from mouse models, the team reported on data from a human clinical trial that revealed two patients with foot ulcers fully recovering after receiving high numbers of CD271-positive stem cells.
“It was quite inspiring to see that one of the patients has recovered enough to return to work,” Inoue says.
Takebe Receives Vilcek Foundation Award for Creative Promise
Organoid research expert Takanori Takebe, MD, PhD, was selected as one of eight people to receive a 2024 Vilcek Foundation Prize in recognition of outstanding immigrant contributions to science, medicine, arts and culture in the United States.
Takebe received a $50,000 prize for Creative Promise in Biomedical Science, which recognizes “early and mid-career immigrant professionals whose work represents a unique approach or perspective, or has had a significant impact in their field of study or practice.”
Learn more about our latest research in organoid and stem cell medicine
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About this blog
The Research Horizons blog features news and insights about the latest discoveries and innovations developed by the scientists of Cincinnati Children's. This blog does not provide medical advice, diagnosis, or treatment.
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