Development of in vitro 3D TissueFlex® islet model for diabetic drug efficacy testing.
Development of in vitro 3D TissueFlex® islet model for diabetic drug efficacy testing.
复制标题
DOI：
10.1371/journal.pone.0072612
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cui Z
中科院分区：
文献类型：
--
作者：
Li Z;Sun H;Zhang J;Zhang H;Meng F;Cui Z
越来越多的人被诊断患有II型糖尿病，这对开发更有效的抗糖尿病药物提出了强烈的需求。然而，昂贵的，伦理上有争议的抗糖尿病化合物的动物筛选并不总是预测人类的反应。在研究中使用基于细胞的体外模型比体内模型具有明显的伦理和成本优势。本研究旨在建立一种体外三维胰岛灌注培养模型（Islet TF），用于维持糖尿病药物疗效试验的活力和功能。简言之，将新鲜分离的大鼠胰岛包封在超纯藻酸盐中，并将包封的胰岛在TissueFlex®（一种多重平行灌注的微生物反应器系统）中培养7天。将在细胞培养板中静态培养的包封胰岛（3D静态）和在悬浮液中培养的胰岛（2D）用作比较。在这项研究中，我们首次证明了胰岛TF模型可以保持体外胰岛活力，更重要的是，在7天的培养期内，胰岛素释放和动态反应方面的功能提高。在传统的2D和3D静态模型中，Islet TF在响应药物和药物剂量方面显示出高灵敏度。应用所建立的胰岛TF模型可以模拟临床实际给药情况，胰岛素释放反应模式与体内实验结果一致。胰岛TF可能是一个更具有预测性的体外模型，用于常规的短期和长期抗糖尿病药物疗效测试。
Increasing individuals diagnosed with type II diabetes pose a strong demand for the development of more effective anti-diabetic drugs. However, expensive, ethically controversial animal-based screening for anti-diabetic compounds is not always predictive of the human response. The use of in vitro cell-based models in research presents obviously ethical and cost advantages over in vivo models. This study was to develop an in vitro three-dimensional (3D) perfused culture model of islets (Islet TF) for maintaining viability and functionality longer for diabetic drug efficacy tests. Briefly fresh isolated rat islets were encapsulated in ultrapure alginate and the encapsulated islets were cultured in TissueFlex®, a multiple, parallel perfused microbioreactor system for 7 days. The encapsulated islets cultured statically in cell culture plates (3D static) and islets cultured in suspension (2D) were used as the comparisons. In this study we demonstrate for the first time that Islet TF model can maintain the in vitro islet viability, and more importantly, the elevated functionality in terms of insulin release and dynamic responses over a 7-day culture period. The Islet TF displays a high sensitivity in responding to drugs and drug dosages over conventional 2D and 3D static models. Actual drug administration in clinics could be simulated using the developed Islet TF model, and the patterns of insulin release response to the tested drugs were in agreement with the data obtained in vivo. Islet TF could be a more predictive in vitro model for routine short- and long-term anti-diabetic drug efficacy testing.
登录
查看更多内容
影响因子：
2.2
作者：
Bentsi-Barnes, Kwamina;Doyle, Maire E.;Al-Abdullah, Ismail H.
通讯作者：
Al-Abdullah, Ismail H.
影响因子：
8.2
作者：
Korbutt, GS;Mallett, AG;Rajotte, RV
通讯作者：
Rajotte, RV
影响因子：
2.8
作者：
Korin, Natanel;Bransky, Avishay;Levenberg, Shulamit
通讯作者：
Levenberg, Shulamit
影响因子：
9.7
作者：
Langlois, Genevieve;Dusseault, Julie;Halle, Jean-Pierre
通讯作者：
Halle, Jean-Pierre
影响因子：
7.7
作者：
LACY, PE;KOSTIANOVSKY, M
通讯作者：
KOSTIANOVSKY, M