title: Recent developments in β-cell differentiation of pluripotent stem cells induced by small and large molecules.
abstract: Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β)-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs) to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate) and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4), epidermal growth factor (EGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), noggin, transforming growth factor (TGF-α), and WNT3A) are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation.
authors.affiliation: Department of Medical Microbiology and Parasitology, Universities Putra Malaysia, Serdang 43400, Selangor, Malaysia. sureshkudsc@gmail.com.
authors.forename: S Suresh
authors.initials: SS
authors.lastname: Kumar
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. aalarfajj@ksu.edu.sa.
authors.forename: Abdullah A
authors.initials: AA
authors.lastname: Alarfaj
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. ammurugan11@gmail.com.
authors.forename: Murugan A
authors.initials: MA
authors.lastname: Munusamy
authors.affiliation: Department of Bioscience, Jacintha Peter College of Arts and Sciences, Ayakudi, Tenkasi, Tamilnadu 627852, India. ranjitspkc@gmail.com.
authors.forename: A J A Ranjith
authors.initials: AJ
authors.lastname: Singh
authors.affiliation: Department of Chemical and Materials Engineering, National Central University, No. 300, Jhongda RD., Jhongli, Taoyuan 32001, Taiwan. chia80403@hotmail.com.
authors.forename: I-Chia
authors.initials: IC
authors.lastname: Peng
authors.affiliation: Department of Basic Science and Department of Surgical Sciences, Ajman University of Science and Technology-Fujairah Campus, P.O. Box 9520, Al Fujairah, United Arab Emirates. priyaganu28@gmail.com.
authors.forename: Sivan Padma
authors.initials: SP
authors.lastname: Priya
authors.affiliation: Department of Medical Microbiology and Parasitology, Universities Putra Malaysia, Serdang 43400, Selangor, Malaysia. rukman@upm.edu.my.
authors.forename: Rukman Awang
authors.initials: RA
authors.lastname: Hamat
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. higuchi@ncu.edu.tw.
authors.forename: Akon
authors.initials: A
authors.lastname: Higuchi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002986:Clinical Trials as Topic; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors