Cells, pancreatic islets, and organoids that evade immune detection and autoimmunity, methods of production and use thereof
A technology for immunological detection, autoimmunity, applied to rejection or autoimmunity. , the field of organ or islet-like organoids, which can solve the problems of immune system detection, injury, destruction, etc.
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Embodiment 1
[0390] Example 1: Generation and Characterization of Pancreatic and Islet Organoids
[0391] Although animal disease models can provide insight into disease pathogenesis, drugs identified from screening using animal models often cannot be adopted in human patients. The generation of functional human organoids offers a new therapeutic strategy for drug screening and disease modeling. This article describes a technique to generate 3D human pancreatic mini-organs or organoids (e.g. HILO) in a dish. Using the described technique, diseases such as human type 2 diabetes can be modeled in vitro to find effective drugs against genetic, patient or environment specific diseases such as human type 2 diabetes.
[0392] Development of a gellan gum-based 3D culture system for β-like cell differentiation
[0393] 3-dimensional (3D) culture systems are known to help promote cell self-organization and integration. Therefore, containing extracellular matrix components such as collagen and fi...
Embodiment 2
[0407] Example 2: Transplanted functional islet organoids rescue type 1 diabetic mice
[0408] As further described in the Examples below, expression of specific functional islet markers such as MAFA, UCN3 and mitochondrial oxidation genes such as ERRγ (Esrrg), Ndufa1, Ndufa12 was observed in hiPSC-derived human islet-like organoids , Cox7a2 and Atp5b. Remarkably, these islet-like organoids were recaptured both in human islet development and in the pathogenesis of diabetes. Transplantation of these functional islet-like organoids rescued type 1 diabetic mice with long survival, rapid angiogenesis, and reduced immune rejection.
Embodiment 3
[0409] Example 3: Wnt proteins in metabolic maturation of islet organoids from iPSCs
[0410] Fltp and Esrrg genes were found to be expressed in iPSC-derived islet organoids after treatment with PBS, WNT3a (500 ng / ml), recombinant human (rh) WNT4 (100 ng / ml), or rhWNT5a (400 ng / ml) (day 21 , no need to co-culture with hADSCs or HUVECs). Response to increased rhWNT4 (0, 10, 25, 50, 100, 200 ng / ml) and rhWNT5a (0, 25, 50, 100, 200, 400 ng / ml). Furthermore, mitochondrial genes involved in oxidative phosphorylation (Cox7a2, Ndufa1, Ndufa7), lactate dehydrogenase (Ldha), and Fltp (Wnt / planar cell polarity (PCP) effector and reporter Gene). In the absence of supportive hADSC or HUVEC, should respond to increasing doses of rhWNT4 (0, 10, 25, 50, 100, 200 ng / ml) and rhWNT5a (0, 25, 50, 100, 200, 400 ng / ml). Mitochondria (Mitotracker; mitochondria red) and insulin (Insulin-GFP) levels were increased in hiPSC-derived islet organoids after treatment with PBS or WNT4 (100 ng / ml) for 8 ...
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