Latest news with #CincinnatiChildrens
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2 days ago
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Liver Organoid Breakthrough: Generating Organ-Specific Blood Vessels
CINCINNATI, June 25, 2025 /PRNewswire/ -- Scientists from Cincinnati Children's and colleagues based in Japan report achieving a major step forward in organoid technology--producing liver tissue that grows its own internal blood vessels. This significant advance could lead to new ways to help people living with hemophilia and other coagulation disorders while also taking another step closer to producing transplantable repair tissues for people with damaged livers. The study, led by Takanori Takebe, MD, PhD, director for commercial innovation at the Cincinnati Children's Center for Stem Cell and Organoid Research and Medicine (CuSTOM), was published online June 25, 2025, in Nature Biomedical Engineering. Co-authors included experts from the Institute of Science Tokyo, the Ichan School of Medicine at Mount Sinai, and Takeda Pharmaceutical Co., which also provided funding for the study. "Our research represents a significant step forward in understanding and replicating the complex cellular interactions that occur in liver development. The ability to generate functional sinusoidal vessels opens up new possibilities for modeling a wide range of human biology and disease, and treating coagulation disorders and beyond," Takebe says. What are organoids? For more than 15 years, researchers at Cincinnati Children's and many other institutions have been working to grow human organ tissue in the laboratory. Such tissues already have become important tools for medical research and may soon become sophisticated enough to be used directly to help repair damaged organs. The complex process involves placing induced pluripotent stem cells (iPSCs) in special gels designed to prompt the stem cells to grow into specific tissue types. The stem cells can be generic or come from specific individuals with health conditions and can be gene-edited before beginning the process. Cincinnati Children's has been a leader in organoid research since 2010 when experts here developed the first functional intestinal organoid grown from iPSCs. Since then, CuSTOM has grown and evolved to include 37 labs across 16 research divisions, where teams are improving organoid technology and using organoids to shed new light on a wide range of diseases and conditions. Overcoming a challenge Until recently, the size of lab-grown organoids has been fundamentally limited because they have not included important tissues that connect organs to the rest of the body; such as nerves and blood vessels. This study recounts how the research team overcame the blood vessel obstacle. The experiments involved required nearly a decade to complete. Ultimately, the project succeeded at differentiating human pluripotent stem cells into CD32b+ liver sinusoidal endothelial progenitors (iLSEP). Then the team used an inverted multilayered air-liquid interface (IMALI) culture system to support the iLSEP cells as they self-organized into hepatic endoderm, septum mesenchyme, arterial, and sinusoidal quadruple progenitors. The advantage of using the iLSEP progenitor cells as building blocks is that they are specific to the liver. Some other studies seeking to add vascularization to organoids have depended upon "fully committed" arterial endothelial cells. These vessels may not function inside an organ as well as progenitor cells from that organ. Location and timing also were crucial to achieving the initial vessel formation. "The success occurred in part because the different cell types were grown as neighbors that naturally communicated with each other to take their next development steps," says the study's first author Norikazu Saiki, PhD, of the Institute of Science Tokyo. Key findings from the research include: Development of Fully Functional Human Vessels: The new method produced "perfused blood vessels with functional sinusoid-like features," which means the vessels were fully open and included the pulsing cell types needed to help blood move through. Correction of Coagulation Disorders: The advanced organoids also generated the correct cell types needed to produce four types of blood coagulation factors, including Factor VIII, which is missing among people with hemophilia A. In mice that mimic hemophilia, the study showed that organoid-derived Factor VIII rescued them from severe bleeding. Potential Application Beyond Liver Organoids: By developing IMALI culture methods for allowing multiple cell types to self-organize naturally, the new technology may open a possibility to grow organ-specific vesselsin other types of organoids. Big Step Closer to Improved Treatments for Hemophilia, Liver Failure In the U.S. an estimated 33,000 males live with hemophilia. Most have hemophilia A (factor VIII deficiency), while a smaller group has hemophilia B (factor IX deficiency). The condition can cause repeated bleeding within joints that can lead to chronic pain and mobility limitations. Hemophilia makes surgery risky and other wounds harder to heal. It also can lead to seizures and paralysis when bleeding affects the brain. Hemophilia is treated by injecting commercially prepared concentrates to replace the missing coagulation factors. However, human blood contains a dozen different clotting factors and there are no available human protein sources for missing coagulation factors V or XI. Also, about 20% of people with hemophilia A develop inhibitors to standard treatment products. "These advanced liver organoids can secrete these coagulation factors. If they can be produced at scale, they could become a viable treatment source that would benefit people who have developed inhibitors or are not indicated for gene therapy," Takebe says. Meanwhile, people experiencing acute or chronic liver failure also do not produce adequate supplies of coagulation factors, placing them at higher risk of bleeding complications during surgery. A factor-secreting organoid 'factory' also could help these patients. Longer-term, increasingly sophisticated liver organoids may eventually supply repair tissues that can help diseased livers heal themselves. About the study Cincinnati Children's co-authors on this study included Kentaro Iwasawa, MD, PhD, and Wendy Thompson, PhD. The Integrative Morphology Core and Pluripotent Stem Cell and Organoid Core at Cincinnati Children's contributed. Funding sources for this research included Takeda Pharmaceutical Company, the Center for iPS Cell Research and Application (CiRA) at Kyoto University, the Mitsubishi Foundation, and awards from the Japan Science and Technology Agency (JST). This work also was supported by an NIH Director's New Innovator Award, P30 DK078392, R01DK135478, and a CURE award from the Cincinnati Children's Research Foundation. View original content to download multimedia: SOURCE Cincinnati Children's Hospital Medical Center Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
2 days ago
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Lab-grown liver grows veins, stops bleeding in mice with engineered clotting proteins
In a breakthrough that brings bioengineered organs one step closer to reality, scientists have created lab-grown liver tissue capable of forming its own blood vessels. A team from Cincinnati Children's Hospital, in collaboration with Japanese researchers, successfully engineered liver organoids that developed spontaneous vascular systems, overcoming a long-standing challenge in tissue engineering. This self-vascularizing liver tissue could pave the way for future transplantable grafts and offer new treatment possibilities for people with hemophilia and other coagulation disorders. Until now, most lab-grown organoids have lacked internal blood vessels, limiting their size, function, and medical potential. By enabling more effective circulation and tissue maturation, the new technique opens the door to growing complex, functional human organs entirely outside the body. "Our research represents a significant step forward in understanding and replicating the complex cellular interactions that occur in liver development,' said Takanori Takebe, director for commercial innovation at the Cincinnati Children's Center for Stem Cell and Organoid Research and Medicine (CuSTOM) and lead author of the study. 'The ability to generate functional sinusoidal vessels opens up new possibilities for modeling a wide range of human biology and disease, and treating coagulation disorders and beyond." At the heart of the process is the use of induced pluripotent stem cells (iPSCs), which are placed in specially formulated gels that guide their development into specific tissue types. These cells can be sourced from healthy donors or patients with particular medical conditions and may be gene-edited to model or correct diseases. To overcome the vascularization barrier, a key obstacle in scaling up organoids, the team spent nearly ten years refining their approach. They began by coaxing iPSCs to differentiate into CD32b+ liver sinusoidal endothelial progenitors (iLSEPs), a type of precursor cell specific to liver blood vessels. These were then introduced into an inverted multilayered air-liquid interface (IMALI) culture system, a setup that encouraged them to self-organize alongside other liver-supportive cells into more complex, layered tissue. The result was a quadruple progenitor mix, including hepatic endoderm, septum mesenchyme, arterial, and sinusoidal cells, that naturally developed into functioning sinusoid-like vessels. Unlike earlier efforts that used fully formed arterial cells, the team's use of liver-specific progenitors allowed for more integrated, lifelike vessel development. Crucially, spatial arrangement and developmental timing also played a role; the proximity of different cell types in the culture system allowed them to interact and mature just as they would in a developing human liver. "The success occurred in part because the different cell types were grown as neighbors that naturally communicated with each other to take their next development steps," says the study's first author, Norikazu Saiki, PhD, of the Institute of Science Tokyo. The vascularized organoids didn't just look more like real liver tissue—they also began to behave like it. The engineered structures produced perfused, sinusoid-like blood vessels that allowed fluid to move through, mimicking the natural rhythm of liver circulation. More remarkably, the organoids also developed the ability to secrete blood-clotting proteins critical for patients with coagulation disorders. Among the factors produced was Factor VIII, a protein missing in people with hemophilia A. When tested in mice engineered to mimic the disease, the organoid-derived Factor VIII was able to correct severe bleeding, offering a proof-of-concept for therapeutic use. The organoids also generated other coagulation-related proteins, suggesting the potential for broader applications in treating patients with rare clotting disorders or acute liver failure. In the U.S. alone, an estimated 33,000 males live with hemophilia, the majority of whom have hemophilia A, caused by a deficiency in Factor VIII. The condition can lead to frequent internal bleeding, especially in joints, resulting in chronic pain, restricted mobility, and long-term damage. More severe cases can pose life-threatening risks, with bleeding episodes in the brain potentially causing seizures or paralysis. If scaled successfully, these self-vascularizing liver organoids could serve as biological factories, producing essential proteins for people who don't respond to standard treatments or who lack access to gene therapy. For those with liver damage, they could someday offer a regenerative option, replacing lost function without requiring a full organ transplant. The full study has been published in Nature Biomedical Engineering.
Yahoo
10-06-2025
- Health
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Children With Acute Allergic Reactions Often Spend Unnecessary Time in Hospitals
While many children experiencing anaphylaxis stay for long hours, even overnight, after receiving a dose of epinephrine, 95% could be safely discharged within 2 hours and 98% within 4 hours, study led by experts at Cincinnati Children's reports CINCINNATI, June 10, 2025 /PRNewswire/ -- Be it peanuts or other triggers, many families live with the day-to-day risk that their child might experience a sudden and scary allergic reaction. In fact, pediatric emergency department visits in the United States to treat acute allergic reactions more than tripled from 2008 to 2016. But once they arrive at the hospital, many children are staying much longer than necessary according to a study involving more than 5,000 children conducted at 31 hospitals in the US and Canada. Findings were published June 10, 2025, in Lancet: Child and Adolescent Health. "Years ago, we used to admit virtually all kids with anaphylaxis to the hospital. We have stopped doing that, but most hospitals still routinely observe kids for over four hours, some even longer. And almost all hospitals admit kids if they have any signs of cardiovascular involvement," says the study's lead author Tim Dribin, MD, an emergency medicine physician at Cincinnati Children's. "Our study suggests that 95% of patients could have been safely discharged two hours after receiving their first epinephrine dose and that 98% could have been safely discharged four hours after the first epinephrine dose." Why so much observation time? The overwhelming majority of children visiting emergency departments for acute allergic reactions can be routinely treated and promptly sent home. In an age where many people with allergies—even young children—carry their own epinephrine injector pens, many situations require no hospital visit at all. However, about 5% of children experience a "biphasic reaction," which means their symptoms can return even though they received an epinephrine injection. In the absence of clear standards, many clinicians choose to keep patients in hospital for long periods of observation just in case. "One concern about biphasic reactions is that the time it takes for symptoms to re-emerge can be highly variable," Dribin says. "This study was designed to take a closer look at this population and determine if children at very low risk can be better identified and discharged safely." Clearing the backup The research team gathered data from 5,641 emergency visits where anaphylaxis was treated with an epinephrine injection. About 90% of the children studied experienced allergic reactions to foods, including peanuts, eggs, milk, shellfish, sesame, gluten and soy. In some cases, the exact food trigger was not known. About 6% involved medication reactions and 3% involved insect stings. While nearly 17% of children were admitted for overnight observation, and others stayed in emergency departments well beyond 4 hours, the need for second doses of epinephrine to cope with biphasic reactions tended to show up quickly. The study found that 4.7% of patients received a second dose within two hours of their initial injection and that 1.9% received a second dose after four hours. Some children clearly needed hospital-level care from the moment they arrived at the hospital. About 1% of all the children studied needed high-acuity services such as ventilators to support breathing. But among the rest of those admitted to hospital beds, most never needed a second epinephrine shot much less intensive care. "We stratified the patients by severity groups and found that patients with no cardiovascular involvement were at low risk of receiving repeat epinephrine beyond 2 hours after the initial epinephrine dose," Dribin says. "Meanwhile even the patients with cardiovascular involvement were at low risk of receiving repeat epinephrine beyond 4 hours." Potential time and resource savings Overall, children with severe allergic reactions represent a modest flow of demand for emergency care. However, having beds occupied for any unnecessary observation periods makes it harder to serve other patients in need. "Pediatric emergency departments can get crowded quite quickly, especially during winter infection season. We need to ensure efficient throughput to allow us to provide access to as many patients as we can," says David Schnadower, MD, MPH, director of the Division of Emergency Medicine at Cincinnati Children's. "An important value of this study is that it was large enough that the results can give clinicians confidence that discharging patients showing no concerning symptoms in less than two hours is going to be safe for most children." The study did not attempt to calculate the potential cost savings that could be achieved because hospital prices and care practices can vary so widely. However, the savings from reducing unnecessary hospital admissions could be substantial, the co-authors say. "I think the bigger impact would be for the patients and families…parents being able to go back to work quicker, children missing less school," Dribin says. "This data allows clinicians to make decisions about observation based on their risk tolerance and that of the patient and the family Some families might feel risk-averse and want to stay a little longer. Others might have another auto injector, and they feel comfortable managing at home. Having that choice is really empowering." Co-author Hugh Sampson, MD, an allergist at the Icahn School of Medicine at Mount Sinai in New York City, agrees. "We also have seen patients and their families avoid or delay going to the emergency department because they didn't want to sit there for hours of observation," Sampson says. "Such delays can prove dangerous. This study's findings support discharging patients more expeditiously, which will likely reduce patient reluctance to seek necessary help." Funding sources for this study included the National Center for Advancing Translational Sciences and The National Institute of Allergy and Infectious Diseases. View original content to download multimedia: SOURCE Cincinnati Children's Hospital Medical Center Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
