Review
Rev Diabet Stud,
2010,
7(2):93-104 |
DOI 10.1900/RDS.2010.7.93 |
The New Generation of Beta-Cells: Replication, Stem Cell Differentiation, and the Role of Small Molecules
Malgorzata Borowiak
Harvard Stem Cell Institute and Department of Stem Cells and Regenerative Biology, 42 Church St, Cambridge, 02138, MA, USA
Manuscript submitted June 21, 2010; resubmitted July 18, 2010; accepted July 30, 2010.
Keywords: stem cell, induced pluripotent, embryonic day, transcription factor, definite endoderm, diabetes, transplantation, Pdx1, beta-cell, growth factor
Abstract
Diabetic patients suffer from the loss of insulin-secreting β-cells, or from an improper working β-cell mass. Due to the increasing prevalence of diabetes across the world, there is a compelling need for a renewable source of cells that could replace pancreatic β-cells. In recent years, several promising approaches to the generation of new β-cells have been developed. These include directed differentiation of pluripotent cells such as embryonic stem (ES) cells or induced pluripotent stem (iPS) cells, or reprogramming of mature tissue cells. High yield methods to differentiate cell populations into β-cells, definitive endoderm, and pancreatic progenitors, have been established using growth factors and small molecules. However, the final step of directed differentiation to generate functional, mature β-cells in sufficient quantities has yet to be achieved in vitro. Beside the needs of transplantation medicine, a renewable source of β-cells would also be important in terms of a platform to study the pathogenesis of diabetes, and to seek alternative treatments. Finally, by generating new β-cells, we could learn more details about pancreatic development and β-cell specification. This review gives an overview of pancreas ontogenesis in the perspective of stem cell differentiation, and highlights the critical aspects of small molecules in the generation of a renewable β-cell source. Also, it discusses longer term challenges and opportunities in moving towards a therapeutic goal for diabetes.
Fulltext:
HTML
, PDF
(256KB)
This article has been cited by other articles:
|
Stemistry: The Control of Stem Cells in Situ Using Chemistry
Davies SG, Kennewell PD, Russell AJ, Seden PT, Westwood R, Wynne GM
J Med Chem 2015. In press
|
|
|
The temporal and hierarchical control of transcription factors-induced liver to pancreas transdifferentiation
Berneman-Zeitouni D, Molakandov K, Elgart M, Mor E, Fornoni A, Domínguez MR, Kerr-Conte J, Ott M, Meivar-Levy I, Ferber S
Plos One 2014. 9(2):e87812
|
|
|
Modeling the blood-brain barrier using stem cell sources
Lippmann ES, Al-Ahmad A, Palecek SP, Shusta EV
Fluids Barriers CNS 2013. 10(1):2
|
|
|
Position Statement of the Chinese Diabetes Society regarding stem cell therapy for diabetes
Zhu D, Chen L, Hong T, Chinese Diabetes Society
J Diabetes 2012. 4(1):18-21
|
|
|
Differentiation of mesenchymal stem cells derived from pancreatic islets and bone marrow into islet-like cell phenotype
Zanini C, Bruno S, Mandili G, Baci D, Cerutti F, Cenacchi G, Izzi L, Camussi G, Forni M
PLoS One 2011. 6(12):e28175
|
|
|
Generation of insulin-producing cells from pluripotent stem cells: from the selection of cell sources to the optimization of protocols
Liew CG
Rev Diabet Sud 2010. 7(2):82-92
|
|
|