Extrinsic Factors Involved in the Differentiation of Stem Cells into Insulin-Producing Cells: An Overview

Table 3

Extrinsic factors involved in insulin-producing cell generation.

Extrinsic factor	Effect	Author
bFGF	Beta-cell differentiation	Dalvi et al., 2009 [49]
	Potent chemoattractant. May be useful in cluster formation	Hardikar et al., 2003 [50]
EGF	High concentration may be inhibitory to beta-cell differentiation	Cras-Méneur et al. 2001 [51], Dalvi et al., 2009 [49]
bFGF and EGF	Differentiation of embryonic stem cells into IPCs	Lumelsky et al., 2001 [52]
	Differentiation of human bone marrow-derived mesenchymal stem cells into IPCs	Sun et al., 2007 [35]
Betacellulin	Formation of islet-like clusters	Demeterco et al., 2000 [53]
	Induction of beta cell differentiation
Activin A	Increase in insulin content	Demeterco et al., 2000 [53]
Betacellulin and activin A	Differentiation of pancreatic acinar AR42J cells into IPCs	Mashima et al., 1996 [54]
	Combined effect may be weaker than that of either factor alone	Demeterco et al., 2000 [53]
	Differentiation of human liver-derived insulin-producing cells toward the beta-cell phenotype	Zalzman et al., 2005 [40]
	Differentiation of human bone marrow-derived mesenchymal stem cells into IPCs	Sun et al., 2007 [35]
Nicotinamide	Differentiation of stem cells of various origins into IPCs	Chen et al., 2004 [44], Segev et al., 2004 [3], Tang et al., 2004 [45], Sun et al., 2007 [35], Sun et al., 2007 [46], Wu et al., 2007 [47], Chao et al., 2008 [48], Gabr et al., 2008 [36], Gao et al., 2008 [37]
	Increase in insulin content, DNA content, expression of insulin, glucagon, and somatostatin genes	Otonkoski et al., 1993 [55]
Exendin-4	Differentiation of murine bone marrow stem cells into IPCs	Tang et al., 2004 [45]
	Formation of insulin-expressing cells generated from adipose tissue-derived mesenchymal stem cells	Timper et al., 2006 [38]
	Differentiation of rat bone marrow-derived mesenchymal stem cells into IPCs	Wu et al., 2007 [47]
	Differentiation of rat bone marrow-derived stem cells into IPCs	Gabr et al., 2008 [36]
	Increase in insulin release by IPCs generated from mouse embryonic stem cells	Li et al., 2010 [56]
Hepatocyte growth factor	Differentiation of pancreatic acinar cells into IPCs	Mashima et al., 1996 [54]
	Increase in the number of IPCs in cultured human islets	Otonkoski et al., 1996 [57]
Gastrin	Stimulation of islet differentiation and islet growth	Wang et al., 1993 [58], Wang et al., 1997 [59]
Glucose	Low concentration (5 mM) increased insulin content.High concentrations (20–30 mM) increased beta cell replication	Bonner-Weir et al., 1989 [60]