title: Development of in vitro 3D TissueFlex® islet model for diabetic drug efficacy testing.
abstract: 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.
authors: Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom.
authors: Zhaohui
authors: Z
authors: Li
authors: He
authors: H
authors: Sun
authors: Jianbin
authors: J
authors: Zhang
authors: Haijiao
authors: H
authors: Zhang
authors: Fanyu
authors: F
authors: Meng
authors: Zhanfeng
authors: Z
authors: Cui
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000379:methods*; D014022:Tissue Survival / Q000187:drug effects; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D014044:Tolbutamide; D005947:Glucose
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