MSGID: 1:317/3 642cf971   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    A miniature heart in a petri dish: Organoid emulates development of the   
   human heart    
      
     Date:   
         April 4, 2023   
     Source:   
         Technical University of Munich (TUM)   
     Summary:   
         A team has induced stem cells to emulate the development of the   
         human heart. The result is a sort of 'mini-heart' known as an   
         organoid. It will permit the study of the earliest development   
         phase of our heart and facilitate research on diseases.   
      
      
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   FULL STORY   
   ==========================================================================   
   A team at the Technical University of Munich (TUM) has induced stem   
   cells to emulate the development of the human heart. The result is a   
   sort of "mini- heart" known as an organoid. It will permit the study   
   of the earliest development phase of our heart and facilitate research   
   on diseases.   
      
      
   ==========================================================================   
   The human heart starts forming approximately three weeks after   
   conception. This places the early phase of heart development in a time   
   when women are often still unaware of their pregnancy. That is one reason   
   why we still have little knowledge of many details of how the heart   
   is formed. Findings from animal studies are not fully transferable to   
   humans. An organoid developed at TUM could prove helpful to researchers.   
      
   A ball of 35,000 cells The team working with Alessandra Moretti, Professor   
   of Regenerative Medicine in Cardiovascular Disease, has developed a method   
   for making a sort of "mini- heart" using pluripotent stem cells. Around   
   35,000 cells are spun into a sphere in a centrifuge. Over a period   
   of several weeks, different signaling molecules are added to the cell   
   culture under a fixed protocol. "In this way, we mimic the signaling   
   pathways in the body that control the developmental program for the   
   heart," explains Alessandra Moretti. The group has now published its   
   work in the journal Nature Biotechnology.   
      
   First-ever "epicardioids" The resulting organoids are about half a   
   millimeter in diameter. Although they do not pump blood, they can be   
   stimulated electrically and are capable of contracting like human heart   
   chambers. Prof. Moretti and her team are the first researchers in the   
   world to successfully create an organoid containing both heart muscle   
   cells (cardiomyocytes) and cells of the outer layer of the heart wall   
   (epicardium). In the young history of heart organoids -- the first were   
   described in 2021 -- researchers had previously created only organoids   
   with cardiomyocytes and cells from the inner layer of the heart wall   
   (endocardium).   
      
   "To understand how the heart is formed, epicardium cells are decisive,"   
   says Dr. Anna Meier, first author of the study. "Other cell types in the   
   heart, for example in connecting tissues and blood vessels, are formed   
   from these cells.   
      
   The epicardium also plays a very important role in forming the   
   heart chambers."  The team has appropriately named the new organoids   
   "epicardioids."  New cell type discovered Along with the method   
   for producing the organoids, the team has reported its first new   
   discoveries. Through the analysis of individual cells they have determined   
   that precursor cells of a type only recently discovered in mice are   
   formed around the seventh day of the development of the organoid. The   
   epicardium is formed from these cells. "We assume that these cells also   
   exist in the human body -- if only for a few days," says Prof. Moretti.   
      
   These insights may also offer clues as to why the fetal heart can   
   repair itself, a capability almost entirely absent in the heart of an   
   adult human.   
      
   This knowledge could help to find new treatment methods for heart attacks   
   and other conditions.   
      
   Producing "personalized organoids" The team also showed that the organoids   
   can be used to investigate the illnesses of individual patients. Using   
   pluripotent stem cells from a patient suffering from Noonan syndrome,   
   the researchers produced organoids that emulated characteristics of   
   the condition in a Petri dish. Over the coming months the team plans to   
   use comparable personalized organoids to investigate other congenital   
   heart defects.   
      
   With the possibility of emulating heart conditions in organoids, drugs   
   could be tested directly on them in the future. "It is conceivable that   
   such tests could reduce the need for animal experiments when developing   
   drugs," says Alessandra Moretti.   
      
   Organoid research is a key research area at TUM The researchers   
   have registered an international patent for the process of creating   
   heart organoids. The Epicardioid model is one of several organoid   
   projects at TUM. At the Center for Organoid Systems work groups from   
   various departments and chairs will collaborate. They will conduct   
   interdisciplinary research into pancreas, brain and heart organoids with   
   state-of-the-art imaging and cellular analysis to study the formation   
   of organs, cancer and neurodegenerative diseases and achieve progress   
   for medicine with human 3D systems.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Heart_Disease # Vioxx # Stroke_Prevention # Stem_Cells   
             o Matter_&_Energy   
                   # Biochemistry # Batteries # Solar_Energy # Graphene   
       * RELATED_TERMS   
             o Heart_rate o Artificial_heart o Coronary_heart_disease o   
             Embryonic_stem_cell o Ischaemic_heart_disease o Defibrillation   
             o CPR o Artery   
      
   ==========================================================================   
   Story Source: Materials provided by   
   Technical_University_of_Munich_(TUM). Note: Content may be edited for   
   style and length.   
      
      
   ==========================================================================   
   Journal References:   
      1. Anna B. Meier, Dorota Zawada, Maria Teresa De Angelis, Laura   
      D. Martens,   
         Gianluca Santamaria, Sophie Zengerle, Monika Nowak-Imialek,   
         Jessica Kornherr, Fangfang Zhang, Qinghai Tian, Cordula M. Wolf,   
         Christian Kupatt, Makoto Sahara, Peter Lipp, Fabian J. Theis,   
         Julien Gagneur, Alexander Goedel, Karl-Ludwig Laugwitz, Tatjana   
         Dorn, Alessandra Moretti.   
      
         Epicardioid single-cell genomics uncovers principles of human   
         epicardium biology in heart development and disease. Nature   
         Biotechnology, 2023; DOI: 10.1038/s41587-023-01718-7   
      2. Dorota Zawada, Jessica Kornherr, Anna B. Meier, Gianluca Santamaria,   
         Tatjana Dorn, Monika Nowak-Imialek, Daniel Ortmann, Fangfang   
         Zhang, Mark Lachmann, Martina Dressen, Mariaestela Ortiz, Victoria   
         L. Mascetti, Stephen C. Harmer, Muriel Nobles, Andrew Tinker, Maria   
         Teresa De Angelis, Roger A. Pedersen, Phillip Grote, Karl-Ludwig   
         Laugwitz, Alessandra Moretti, Alexander Goedel. Retinoic acid   
         signaling modulation guides in vitro specification of human heart   
         field-specific progenitor pools.   
      
         Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-36764-x   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/04/230404114235.htm   
      
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