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3 Indeed, personalized gut organoids from cystic fibrous patients have been used to screen potential drugs, and liver buds have successfully been used to correct toxic liver failure in mice. 7-8 Therapeutically, organoids could be used to grow new organs from a patient’s own cells for transplantation or to evaluate possible treatment strategies by testing organoids derived from patient tissues. 6 There is also significant interest in utilizing human liver and kidney organoids in drug toxicity testing, where roughly 90% of drugs that pass the current rat toxicity model ultimately fail in clinical trials. 5For example, human cerebral organoids have been investigated as a potential model for neurodevelopment. These unique morphological and cellular properties make organoids an excellent model to study development, infectious disease, and signaling pathways. 1-3 Their self-assembled morphological structure and heterogeneous cellular composition mimic that of in vivo tissues and set it apart from flat homogenous cell lines. Organoids have successfully been cultured from various mouse and human stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult primary tissue. Organoids are stem cell-derived three-dimensional cellular clusters that serve as in vitro surrogates to an entire organ or organ segment. Keywords:Organoids NMR Metabolomics Spectroscopy Pancreas Intestine Metabolic recapitulation Introduction
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Appreciable modifications to the organoid cultivation process are needed if organoids are to realize their full potential in studying the functional properties of the organs they mimic and preemptively assessing an organ’s response to therapy. Our conclusion is that organoids do not accurately recapitulate the metabolism of the organs from which they are derived. Pronounced downregulation (~ an order of magnitude in organ-to-organoid concentration ratio) is observed in both the creatinine catabolic pathway and the choline pathway. This study shows that metabolism is significantly downregulated in the organoids relative to their respective organ system. Since metabolism is a downstream effect relative to genomics, transcriptomics, and proteomics, we have employed high-resolution 1H NMR spectroscopy to observe the water-soluble metabolome and quantify how well organoids represent normal organ metabolism in two organoid-organ systems: the small intestine and the pancreas. While it is known that organoids recapture organ microanatomy, how well they mimic organ function is currently unknown. They demonstrate excellent potential to study development, infectious disease, signaling pathways, drug toxicity, and the efficacy of various therapeutic agents. Organoids are three-dimensional organ buds that are grown via stem cell cultivation and successfully recapitulate the microanatomy of the organs from which they are derived. (2017) Can an Organoid Recapitulate the Metabolome of its Parent Tissue? A Pilot NMR Spectroscopy Study.J Cancer Prev Curr Res 8(7): 00307. Received: Decem| Published: December 21, 2017Ĭitation: Weygand J, Carter SE, Salzillo TC, Moussalli M, Dai B et al. Sarah E Carter, 1 Travis C Salzillo, 1 Micheline Moussalli, 1 Bingbing Dai, 1,2 Prasanta Dutta, 1 Xiangsheng Zuo, 1,2 Jason B Fleming, 3 Imad Shureiqi, 4 Pratip Bhattacharya 3ġDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, USAĢGraduate School of Biomedical Sciences, The University of Texas Health Science Center, USAģDepartment of Pathology, The University of Texas MD Anderson Cancer Center, UASĤDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, USAĥDepartment of Gastrointestinal (GI) Medical Oncology, The University of Texas MD Anderson Cancer Center, USAĦDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USAĬorrespondence: Frances Johnson, 2951 Marina Bay 130-518, League City Texas, Tel 9810368354, Fax 98 401, Tel 28 Please type the correct Captcha word to see email ID. Regret for the inconvenience: we are taking measures to prevent fraudulent form submissions by extractors and page crawlers.