Development of in vitro three-dimensional co-culture system for metabolic syndrome therapeutic agents.
Diabetes Obes Metab
; 21(5): 1146-1157, 2019 05.
Article
in En
| MEDLINE
| ID: mdl-30609258
ABSTRACT
AIMS:
There are many obstacles to overcome in the development of new drugs for metabolic diseases, including efficacy and toxicity problems in later stages of drug development. To overcome these problems and predict efficacy and toxicity in early stages, we constructed a new model of insulin resistance in terms of communication between 3T3-L1 adipocytes and RAW264.7 macrophages by three-dimensional (3D) culture.RESULTS:
In this study, results focused on the functional resemblance between 3D co-culture of adipocytes and macrophages and adipose tissue in diabetic mice. The 3D mono-culture preadipocytes showed good cell viability and induced cell differentiation to adipocytes, without cell confluence or cell-cell contact and interaction. The 3D co-cultured preadipocytes with RAW264.7 macrophages induced greater insulin resistance than two-dimensional and 3D mono-cultured adipocytes. Additionally, we demonstrated that 3D co-culture model had functional metabolic similarity to adipose tissue in diabetic mice. We utilized this 3D co-culture system to screen PPARγ antagonists that might have potential as therapeutic agents for diabetes as demonstrated by an in vivo assay.CONCLUSION:
This in vitro 3D co-culture system could serve as a next-generation platform to accelerate the development of therapeutics for metabolic diseases.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Metabolic Syndrome
/
PPAR gamma
/
Tissue Culture Techniques
/
Drug Evaluation, Preclinical
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Diabetes Obes Metab
Journal subject:
ENDOCRINOLOGIA
/
METABOLISMO
Year:
2019
Document type:
Article
Country of publication:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM