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1.
Curr Drug Targets ; 19(13): 1463-1477, 2018.
Article in English | MEDLINE | ID: mdl-29874998

ABSTRACT

Diabetes mellitus is one of the leading causes of death worldwide. Loss and functional failure of pancreatic ß-cells, the parenchyma cells in the islets of Langerhans, progress diabetes mellitus. The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional ß-cells for treating diabetes mellitus. Human induced Pluripotent Stem Cells (hiPSC), hold potential for treating diabetes ownig to their self-renewal capacity and the ability to differentiate into ß- cells. iPSC technology also provides unlimited starting material to generate differentiated cells for regenerative applications. Progress has also been made in establishing in-vitro culture protocols to yield definitive endoderm, pancreatic endoderm progenitor cells and ß-cells via different reprogramming strategies and growth factor supplementation. However, these generated ß-cells are still immature, lack functional characteristics and exhibit lower capability in reversing the diseases conditions. Current methods employed to generate mature and functional ß-cells include; use of small and large molecules to enhance the reprogramming and differentiation efficiency, 3D culture systems to improve the functional properties and heterogeneity of differentiated cells. This review details recent advancements in the generation of mature ß-cells by reprogramming stem cells into iPSCs that are further programmed to ß-cells. It also provides deeper insight into current reprogramming protocols and their efficacy, focusing on the underlying mechanism of chemical-based approach to generate iPSCs. Furthermore, we have highlighted the recent differentiation strategies both in-vitro and in-vivo to date and the future prospects in the generation of mature ß-cells.


Subject(s)
Diabetes Mellitus/therapy , Induced Pluripotent Stem Cells/cytology , Insulin-Secreting Cells/transplantation , Insulin/metabolism , Animals , Cell Differentiation , Cells, Cultured , Cellular Reprogramming/drug effects , Diabetes Mellitus/metabolism , Humans , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Regenerative Medicine , Signal Transduction , Small Molecule Libraries/pharmacology
2.
Carbohydr Polym ; 134: 799-807, 2015 Dec 10.
Article in English | MEDLINE | ID: mdl-26428187

ABSTRACT

We developed tricalcium phosphate-chitosan-fucoidan biocomposite scaffold (TCP-Ch-Fu) by using the freeze-drying technique. The fabricated biocomposite scaffolds were analyzed by spectroscopy and porosity measurement. The biomechanical properties of scaffolds were assessed by compression test and the results suggested that the incorporation of Fucoidan into the biocomposite improves the compression strength of scaffolds. Biomineralization of scaffolds was evaluated by soaking them in simulated body fluid and the results revealed that the addition of Fucoidan into the scaffolds enhanced the formation of apatite layer on the surface of biocomposite after 7 days of immersion. Alamar Blue assay confirmed that the cell viability of human-derived bone marrow stromal cell was superior in the TCP-Ch-Fuscaffold. The addition of Fucoidan to TCP-Ch increased the release of osteocalcin, confirming that it can support osteogenic differentiation of human mesenchymal stromal cells in in vitro culture. Thus, TCP-Ch-Fu could be a potential candidate for bone-tissue engineering applications.


Subject(s)
Biocompatible Materials/chemistry , Bone and Bones/cytology , Calcium Phosphates/chemistry , Chitosan/chemistry , Polysaccharides/chemistry , Tissue Engineering/methods , Biocompatible Materials/pharmacology , Biomarkers/metabolism , Bone and Bones/drug effects , Cell Differentiation/drug effects , Cell Survival/drug effects , Freeze Drying , Gene Expression Regulation/drug effects , Humans , Mechanical Phenomena , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Minerals/metabolism , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , Porosity , Tissue Scaffolds/chemistry
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