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hiPSCs來源的微工程多類器官系統重現正常和2型糖尿病的患者的肝-胰島軸</span> </div> <div class="right_content"> <div class="art-cont"> <h1 class="art-title">hiPSCs來源的微工程多類器官系統重現正常和2型糖尿病的患者的肝-胰島軸</h1> <div class="art-info"> 發布時間： 2023-09-25　　點擊次數： 182次 </div> <div class="art-body"> <p style="text-align:center"><br/></p><section data-role="outer" label="edit by 135editor"><section><section data-tools="135編輯器" data-id="121531"><section><section><section data-autoskip="1"><section data-role="paragraph"><section><section data-autoskip="1"><p style="text-align: left; margin-bottom: 10px;">2021年12月23日，中國科學院 Jianhua Qin團隊在Advanced Science 期刊上發表了題為“Microengineered Multi-Organoid System from hiPSCs to Recapitulate Human Liver-Islet Axis in Normal and Type 2 Diabetes。該研究開發了一種新的微流體多器官系統，這種新型的多器官系統能夠在體外模擬人體肝臟-胰島軸及其在生理和病理條件下的糖刺激響應，為未來的2型糖尿?。═2DM）研究和藥物開發提供了平臺。</p><p><br style="margin: 0px 0px 10px; padding: 0px; outline: 0px; max-width: 100%; visibility: visible; box-sizing: border-box !important; overflow-wrap: break-word !important; text-align: left;"/></p><p style="text-align:center"><img data-backh="263" data-backw="526" data-cropselx1="0" data-cropselx2="526" data-cropsely1="0" data-cropsely2="263" data-ratio="0.5005740528128588" data-src="https://mmbiz.qpic.cn/sz_mmbiz_png/SJyibI36BxE0KFianc1HYCVnCbdR9kJZWnClwzicZyV8gQmUiaU2ESlW0U5tGW983sa0dBd9Pg6TO52icPezCaFbiaLA/640?wx_fmt=png" data-type="png" data-w="871" data-index="2" src="https://img54.chem17.com/9/20230925/638312517358069460888.png" _width="100%" crossorigin="anonymous" alt="圖片" data-fail="0" style="margin: 0px; padding: 0px; outline: none 0px !important; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; vertical-align: inherit; height: auto !important; max-inline-size: 100%; cursor: pointer; visibility: visible !important; width: 625px;"/></p><section data-role="title" data-tools="135編輯器" data-id="129931"><section><section><section><strong><span style="font-size: 16px;">1 背景介紹</span></strong></section></section></section></section><p style="text-align: left; margin-bottom: 10px;">T2DM是一種系統性多器官代謝性疾病，其特征是不同器官組織之間的動態相互作用，包括肝臟、胰島、脂肪和肌肉。肝臟和胰腺是參與生理葡萄糖穩態的兩個關鍵器官，它們之間的相互作用極大地幫助了血糖水平的正常調節。在禁食狀態下，胰島α-細胞分泌胰高血糖素，并誘導肝臟產生葡萄糖，為重要器官提供能量。餐后，胰島β-細胞分泌胰島素誘導肝臟攝取葡萄糖并促進葡萄糖分解。這些協調的器官間相互作用的被打破可能導致葡萄糖水平失調和代謝紊亂，從而引起T2DM。<br style="margin: 0px 0px 10px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; text-align: left;"/></p><p><br/></p><p style="text-align: left; margin-bottom: 10px;">目前研究葡萄糖代謝和T2DM的藥物篩選在很大程度上依賴于動物模型。然而，由于物種間差異，動物模型不能準確地代表人類生理學。由于多種激素和營養素能協調器官間作用，區分單一因素對體內器官系統的直接和間接影響仍然具有挑戰性。此外，迄今為止，對體外不同組織之間相互作用的研究僅限于細胞共培養。先前研究利用原代動物肝細胞和胰島β-細胞或細胞系的混合物來進行細胞共培養，但它們并不能精確表現人體器官的特異性特征，也不能準確地概括體內信號反饋回路。由于T2DM發病率的增加，科研人員需要開發用于疾病研究和藥物治療的體外人類相關模型。</p><p><br style="margin: 0px 0px 10px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; text-align: left;"/></p><section data-role="title" data-tools="135編輯器" data-id="129931"><section><section><section><span style="font-size: 16px;"><strong>2 研究思路</strong></span></section></section></section></section><p style="text-align: left; margin-bottom: 10px;">首先，研究人員建立了人類誘導多能干細胞（hiPSCs）衍生的肝臟和胰島類器官。</p><p><br style="margin: 0px 0px 10px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; text-align: left;"/></p><p style="text-align:center"><img data-backh="408" data-backw="526" data-cropselx1="0" data-cropselx2="526" data-cropsely1="0" data-cropsely2="408" data-ratio="0.7759259259259259" data-src="https://mmbiz.qpic.cn/sz_mmbiz_jpg/SJyibI36BxE0KFianc1HYCVnCbdR9kJZWnnRMZZEyuDibqueVF9Y7DStsmLnmzCYdg0BlNJia0LYcynqgUmJAhib5yQ/640?wx_fmt=jpeg" data-type="png" data-w="1080" data-index="3" src="https://img53.chem17.com/9/20230925/638312517359722335871.jpg" _width="100%" crossorigin="anonymous" alt="圖片" data-fail="0" style="margin: 0px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; vertical-align: inherit; height: auto !important; width: 625px; visibility: visible !important;"/></p><section style="text-align: center;">圖1：肝臟類器官與胰島類器官的合成</section><p><br/></p><p style="text-align: left; margin-bottom: 10px;"> </p><p style="text-align: left; margin-bottom: 10px;">在確定肝臟類器官與胰島類器官的成功建立后，研究人員利用類器官芯片中的共培養實驗裝置來支持兩種類器官的共同培養，并且研究這兩種類器官共同培養后的生長情況。實驗結果表明該共培養體系有利于維持肝和胰島類器官活性，并增強肝和胰島類器官的分泌功能，提高類器官特異性功能基因和蛋白表達。糖耐受實驗（GTT）結果顯示，共培養體系中的胰島類器官分泌胰島素以響應葡萄糖并促進肝臟葡萄糖攝取。此外，在共培養系統中，葡萄糖水平下降得更快，并在24小時后恢復到正常禁食水平，這在單器官培養中沒有觀察到。</p><p style="text-align:center"><img data-backh="580" data-backw="526" data-cropselx1="0" data-cropselx2="526" data-cropsely1="0" data-cropsely2="580" data-ratio="1.1027777777777779" data-src="https://mmbiz.qpic.cn/sz_mmbiz_jpg/SJyibI36BxE0KFianc1HYCVnCbdR9kJZWnQgqynCbCuZI4PzszLJ95zqevUSvceIZG8QC9e5lMyhrZGyozZnoN3Q/640?wx_fmt=jpeg" data-type="png" data-w="1080" data-index="4" src="https://img56.chem17.com/9/20230925/638312517362866741100.jpg" _width="100%" crossorigin="anonymous" alt="圖片" data-fail="0" style="margin: 0px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; vertical-align: inherit; height: auto !important; width: 625px; visibility: visible !important;"/></p><p style="text-align: center; margin-bottom: 10px;">圖2：肝臟類器官與胰島類器官的共培養</p><p><br/></p><p style="text-align: left; margin-bottom: 10px;"><br/></p><p style="text-align: left; margin-bottom: 10px;">最后，研究人員評估了在高血糖與二甲雙胍干預的狀態下，胰島-肝類器官的線粒體功能和葡萄糖轉運能力。當施加高糖濃度條件后（25mM)，肝和胰島類器官出現明顯的線粒體損傷和葡萄糖轉運功能下降等異常改變。這些病理變化可以通過添加二甲雙胍來緩解，二甲雙胍是一種廣泛用于治療糖尿病的藥物，這表明這種肝-胰島類器官系統有能力模擬T2DM的關鍵病理特征。</p><p><br style="margin: 0px 0px 10px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; text-align: left;"/></p><p style="text-align:center"><img data-backh="336" data-backw="526" data-cropselx1="0" data-cropselx2="526" data-cropsely1="0" data-cropsely2="336" data-ratio="0.6388888888888888" data-src="https://mmbiz.qpic.cn/sz_mmbiz_png/SJyibI36BxE0KFianc1HYCVnCbdR9kJZWnWCtiaXDvaJibwDkm9kkVBDOsc9icVuz2N1KIR4aL8ZOiatU6maxm9hN9kA/640?wx_fmt=png" data-type="png" data-w="1080" data-index="5" src="https://img45.chem17.com/9/20230925/638312517367393751379.png" _width="100%" crossorigin="anonymous" alt="圖片" data-fail="0" style="margin: 0px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; vertical-align: inherit; height: auto !important; width: 625px; visibility: visible !important;"/></p><p style="text-align: left; margin-bottom: 10px;">圖3：評估胰島-肝類器官系統中線粒體功能和葡萄糖轉運能力對高血糖狀態和二甲雙胍治療的反應。</p><p><br/></p><section data-role="title" data-tools="135編輯器" data-id="129931"><section><section><p><span style="font-size: 16px;"><br/></span></p><p><strong><span style="font-size: 16px;">3 研究結論</span></strong></p></section></section></section><p><br/></p><p style="text-align: left; margin-bottom: 10px;">總之，科研人員將類器官與器官芯片前沿技術結合，構建了由人多能干細胞衍生的肝-胰島類器官互作體系。該系統的明顯優勢在于它能夠模擬肝臟和胰島器官對外部高血糖的刺激和藥物反應，而細胞模型和動物模型不容易對其進行研究。未來，這種多器官系統可能與大腦、肌肉和脂肪等其他器官整合，以反映人體的系統生理和病理。</p><p><br style="margin: 0px 0px 10px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; text-align: left;"/></p><p style="text-align:center"><img data-backh="624" data-backw="526" data-ratio="1.1861111111111111" data-src="https://mmbiz.qpic.cn/sz_mmbiz_png/SJyibI36BxE0KFianc1HYCVnCbdR9kJZWnkmKZpQXicndd0Iiabic8B0b4jVjOQMJQ5A7ORFZ4I5Pq27hSHG74K3RgA/640?wx_fmt=png" data-type="png" data-w="1080" data-index="6" src="https://img42.chem17.com/9/20230925/638312517371845196332.png" _width="100%" crossorigin="anonymous" alt="圖片" data-fail="0" style="margin: 0px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; vertical-align: inherit; height: auto !important; width: 625px; visibility: visible !important;"/></p><section data-role="title" data-tools="135編輯器" data-id="129931"><section><section><section><strong><span style="font-size: 16px;">4 原文鏈接</span></strong></section></section></section></section><section>DOI:https://doi.org/10.1002/advs.202103495</section><section data-role="paragraph"><p><br style="margin: 0px 0px 10px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; text-align: left;"/></p></section><section data-role="title" data-tools="135編輯器" data-id="129931"><section><section><section><strong><span style="font-size: 16px;">5 關于?；?/span></strong></section></section></section></section><p style="text-align: left; margin-bottom: 10px;">廈門?；锟萍加邢薰?nbsp;(Xiamen Mogengel) 位于中國·廈門國家高新技術創業中心。公司致力于3D細胞培養核心原材料的研發與產業化升級。目前公司的產品有基質膠、類器官培養基、細胞因子、3D細胞培養耗材、3D細胞培養智能顯微鏡等。公司擁有4大技術研發中心：分子克隆和細胞編輯中心、實驗動物中心、蛋白表達和純化平臺、類器官質檢系統和自動化。</p><p><br style="margin: 0px 0px 10px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; text-align: left;"/></p><p style="text-align: left; margin-bottom: 10px;">團隊擁有十余年類器官技術研究基礎，實力雄厚，科研意志堅定，學術態度嚴謹，大膽嘗試，勇于創新。公司推出的基質膠、類器官培養試劑盒等產品廣泛適用于類器官培養、血管生成實驗、細胞侵襲 (transwell) 實驗、PDX、CDX模型實驗、腫瘤球培養、腫瘤移植、皮下成瘤實驗、干細胞培養及細胞分化研究以及其他待開發實驗類型。</p></section></section></section></section></section></section></section></section></section> </div> <div class="art-next"> <dl class="shangxia"> <dd>上一篇：<a href="/Article-3499294.html">高濃度基質膠能夠為細胞提供附著和生長的表面</a></dd> <dd>下一篇：<a href="/Article-3486734.html">【文獻速遞】通過Hippo-YAP信號通路探究維生素D缺乏引起的大鼠胎兒生長受限</a></dd> </dl> </div> </div> </div> </div> </div> </div> <div id="clear"></div>  <div class="foot_box"> <div class="foot_t"> <div class="w1200"> <a 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