3-D physiomimetic extracellular matrix hydrogels provide a supportive microenvironment for rodent and human islet culture.
3-D physiomimetic extracellular matrix hydrogels provide a supportive microenvironment for rodent and human islet culture.
复制标题
3-D生理模拟的细胞外基质水凝胶为啮齿动物和人类胰岛培养提供了支撑性的微环境。
DOI：
10.1016/j.biomaterials.2018.08.057
复制
发表时间：
2019-04
期刊：
影响因子：
14
通讯作者：
Stabler CL
中科院分区：
文献类型：
--
作者：
Jiang K;Chaimov D;Patel SN;Liang JP;Wiggins SC;Samojlik MM;Rubiano A;Simmons CS;Stabler CL
芯片上器官平台作为具有成本效益的试验平台，用于筛选药物制剂，模拟自然生理学和研究疾病。在糖尿病领域，芯片上胰岛平台的开发将对理解疾病病理学和发现潜在疗法产生广泛影响。然而，胰岛微生理学系统受限于其在培养中的差的细胞存活和功能。与这种下降有关的一个关键因素是隔离后胰岛-基质相互作用的破坏。在此，我们试图使用脱细胞细胞外基质（ECM）水凝胶来概括体内胰岛周围生态位。来源于猪膀胱、肺和胰腺组织，使用啮齿动物和人胰岛生成、表征和验证3-D ECM水凝胶。优化的脱细胞方案导致水凝胶具有与其基质组成相关的独特粘弹性。ECM水凝胶内的人或大鼠胰岛的原位3-D包封导致在标准培养条件下改善的功能稳定性。胰岛组成和形态也发生了改变，胰岛驻留内皮细胞的保留增强，以及从胰岛球体中出现的索状结构或芽的形成。这些支持性3-D仿生ECM水凝胶可以在微流体平台内用于胰岛的长期培养。
Organ-on-a-chip platforms serve as cost-efficient testbeds for screening pharmaceutical agents, mimicking natural physiology, and studying disease. In the field of diabetes, the development of an islet-on-a-chip platform would have broad implications in understanding disease pathology and discovering potential therapies. Islet microphysiological systems are limited, however, by their poor cell survival and function in culture. A key factor that has been implicated in this decline is the disruption of islet-matrix interactions following isolation. Herein, we sought to recapitulate the in vivo peri-islet niche using decellularized extracellular matrix (ECM) hydrogels. Sourcing from porcine bladder, lung, and pancreas tissues, 3-D ECM hydrogels were generated, characterized, and validated using both rodent and human pancreatic islets. Optimized decellularization protocols resulted in hydrogels with distinctive viscoelastic properties that correlated to their matrix composition. The in situ 3-D encapsulation of human or rat islets within ECM hydrogels resulted in improved functional stability over standard culture conditions. Islet composition and morphology were also altered, with enhanced retention of islet-resident endothelial cells and the formation of cord-like structures or sprouts emerging from the islet spheroid. These supportive 3-D physiomimetic ECM hydrogels can be leveraged within microfluidic platforms for the long-term culture of islets.
登录
查看更多内容
影响因子：
4.8
作者：
Farilla, L;Bulotta, A;Perfetti, R
通讯作者：
Perfetti, R
影响因子：
14
作者：
Brown, Bryan N.;Valentin, Jolene E.;Stewart-Akers, Ann M.;McCabe, George P.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
14
作者：
Faulk DM;Londono R;Wolf MT;Ranallo CA;Carruthers CA;Wildemann JD;Dearth CL;Badylak SF
通讯作者：
Badylak SF
DOI：
10.1073/pnas.97.14.7999
发表时间：
2000-07-05
影响因子：
11.1
作者：
Bonner-Weir, S;Taneja, M;O'Neil, JJ
通讯作者：
O'Neil, JJ
影响因子：
6.2
作者：
Gaber, AO;Fraga, DW;Kotb, MY
通讯作者：
Kotb, MY