This technology is a method to generate squamous epithelial 3D organoids that can mimic the natural physiology of tissues and be used to model gastrointestinal physiology.
Unmet Need: Platform for predicting patient-specific treatment outcomes in squamous epithelia
Current methods in moving towards personalized medicine include using patient-specific organoids to understand patient-specific genetic and molecular makeup. However, most of these organoids have limited capability to predict treatment responses in diseases involving squamous epithelia. As a result, there exists a need to model squamous epithelial pathologies in personalized medicine that involves drug testing and evaluation of disease susceptibility. Squamous epithelial 3D-organoids can mimic the natural physiology of epithelial tissues and model the gastrointestinal physiology needed to understand the progression of diseases that occur in squamous epithelia.
The Technology: 3D squamous epithelial organoids for personalized and predictive medicine
This technology describes the composition and tissue engineering method to generate squamous epithelial 3D organoids. These organoids, which can be generated in 14 days, mimic native epithelial gastrointestinal physiology and can be used to predict treatment response. This technology can serve as an experimental platform to study genetic and environmental factors in the development and progression of diseases occurring in squamous epithelia for specific patients.
This technology has been validated with human and mouse tissue.
Applications:
- Esophageal organogenesis model
- Research tool for esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC)
- Research tool for studying squamous epithelial diseases
Advantages:
- Can be personalized for specific patients
- Can be grown within 14 days
- Models squamous epithelial physiology and pathology
- Can be integrated with clinical data
- Compatible with human and mice
- Rapid ex vivo evaluation of therapeutic effects of drugs
- Can be made from normal pre-neoplastic epithelia and other benign conditions such as esophagitis
Lead Inventor:
Anil K. Rustgi, MD
Patent Information:
Patent Pending(WO/2023/230297)
Related Publications:
Karakasheva TA, Gabre JT, Sachdeva UM, Cruz-Acuña R, Lin EW, DeMarshall M, Falk GW, Ginsberg GG, Yang Z, Kim MM, Diffenderfer ES, Pitarresi JR, Li J, Muir AB, Hamilton KE, Nakagawa H, Bass AJ, Rustgi AK. “Patient-derived organoids as a platform for modeling a patient's response to chemoradiotherapy in esophageal cancer” Sci Rep. 2021 Oct 29; 11(1): 21304.
Karakasheva TA, Kijima T, Shimonosono M, Maekawa H, Sahu V, Gabre JT, Cruz-Acuña R, Giroux V, Sangwan V, Whelan KA, Natsugoe S, Yoon AJ, Philipone E, Klein-Szanto AJ, Ginsberg GG, Falk GW, Abrams JA, Que J, Basu D, Ferri L, Diehl JA, Bass AJ, Wang TC, Rustgi AK, Nakagawa H. “Generation and Characterization of Patient-Derived Head and Neck, Oral, and Esophageal Cancer Organoids” Curr Protoc Stem Cell Biol. 2020 Jun; 53(1): e109
Kijima T, Nakagawa H, Shimonosono M, Chandramouleeswaran PM, Hara T, Sahu V, Kasagi Y, Kikuchi O, Tanaka K, Giroux V, Muir AB, Whelan KA, Ohashi S, Naganuma S, Klein-Szanto AJ, Shinden Y, Sasaki K, Omoto I, Kita Y, Muto M, Bass AJ, Diehl JA, Ginsberg GG, Doki Y, Mori M, Uchikado Y, Arigami T, Avadhani NG, Basu D, Rustgi AK, Natsugoe S. “Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells” Cell Mol Gastroenterol Hepatol. 2018 Sep 14; 7(1): 73-91
Kasagi Y, Chandramouleeswaran PM, Whelan KA, Tanaka K, Giroux V, Sharma M, Wang J, Benitez AJ, DeMarshall M, Tobias JW, Hamilton KE, Falk GW, Spergel JM, Klein-Szanto AJ, Rustgi AK, Muir AB, Nakagawa H. “The Esophageal Organoid System Reveals Functional Interplay Between Notch and Cytokines in Reactive Epithelial Changes” Cell Mol Gastroenterol Hepatol. 2018 Jan 3; 5(3): 333-352
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