TABLE 1.
Summary of studies using PDX1 in obtaining β-cells (full version Supplementary Material).
| Study | Cell source | Transcription factors | Small molecules | Outcome |
|---|---|---|---|---|
| Differentiated adult cells | ||||
| (Ferber et al. 2000) | mouse liver cells | PDX1 | N/A | Insulin secretion |
| (Ber et al. 2003) | mouse liver cells | PDX1 | N/A | Induction of pancreatic Exocrine and endocrine genes, insulin secretion |
| (Imai et al., 2005, Kaneto et al., 2005, Cao et al., 2004, Tang et al., 2006) | mouse liver cells | PDX1-VP16 PDX1 | N/A | Expression of pancreatic markers, insulin secretion |
| (Wang et al. 2007) | mouse liver cells | PDX1-NGN3 | N/A | Insulin secretion, near normal GSIT function |
| (Zhou et al. 2008) | mouse pancreatic exocrine cells | PDX1- MAFA-NGN3 | N/A | Adoption of β-cells morphology and marker expression, insulin secretion |
| (Banga et al. 2012) | mouse hepatic duct-like cells | PDX1-MAFA- NGN3 | N/A | Adoption of β-cells morphology and marker expression, insulin secretion |
| (Cim et al. 2012) | rat liver cells | PDX1-NGN3-MAFA | N/A | Expression of insulin mRNA |
| (Hickey et al. 2013) | mouse gall bladder epithelial cells | PDX1-MAFA-NGN3 | retinoic acid, dibenzazepine | Upregulation of β-cells genes, insulin secretion |
| (Akinci et al. 2013) | rat pancreatic exocrine cells and hepatocytes mouse hepatocyte-derived small cells | PDX1-MAFA-NGN3 | DAPT, BIX-01294, NECA | Increased expression of β-cell markers, insulin secretion |
| (Chen et al. 2014) | mouse intestine crypts cells | PDX1-MAFA-NGN3 | N/A | Adoption of β-cells morphology, insulin secretion |
| (Cardinale et al. 2015) | human biliary tree stem cells | PDX1 | bFGF, PDX-1 peptide | Increased expression of β-cells markers, insulin and C-peptide secretion |
| (Lima et al. 2016) | human exocrine pancreatic cells | PDX1-NGN3-MAFA-PAX4 | ITS, 5-aza-2′-deoxycytidine, sodium butyrate, SB431542, Y27632, betacellulin, exendin-4, nicotinamide | Insulin packaging and secretion |
| (Xiao et al. 2018) | mouse pancreatic alpha cells | PDX1-MAFA | N/A | Increased β-cell mass, insulin secretion |
| Embryonic stem cells | ||||
| (Xu et al. 2013) | mouse ESCs | PDX1-MAFA- NEUROD-NGN3 | β-mercaptoethanol, activin A, retinoic acid, ITS, bFGF, EGF, N2, B27, nicotinamide | Increased expression of β-cells markers, insulin secretion |
| (Salguero-Aranda et al. 2016) | mouse ESCs | increased PDX1 expression by small molecules | DETA-NO, valproic acid, P300 inhibitor C646, β-mercaptoethanol | Increased expression of β-cells markers, glucose responsivity, insulin secretion |
| Induced pluripotent stem cells | ||||
| (Saxena et al. 2016) | human iPSCs | PDX1-MAFA- NGN3 | Activin A, wnt3A, bFGF, BMP4, VEGF, noggin, FGF10, KGF, EGF, B27, ascorbic acid, KAAD-cyclopamine, retinoic acid, Y-27632, vitamin A, T3, Alk5 inhibitor, dibenzazepine | Adoption of β-cells morphology, insulin secretion |
| (Rajaei et al. 2018) | human iPSCs | PDX1 | activin A, Wnt3a, KGF, EGF, SB431542, B27, KAAD cyclopamine, retinoic acid, noggin, IBMX | Insulin and C-peptide secretion, adoption of β-cells morphology |
| Mesenchymal stem cells | ||||
| (Yuan et al. 2010) | rat bone marrow-derived MSCs | PDX1 | N/A | Acquisition of β-cells phenotype, insulin secretion |
| (He et al. 2011) | human umbilical cord MSCs | PDX1 | EGF, B27, GLP-1, betacellulin, HGF, nicotinamide, β-mercaptoethanol | Adoption of β-cells morphology and marker expression, insulin and C-peptide secretion |
| (Lima et al. 2013) | human exocrine pancreas-derived MSCs | PDX1-MAFA-NGN3-PAX4 | betacellulin, exendin-4, nicotinamide | Insulin secretion |
| (Chun et al. 2015) | human amniotic fluid-derived MSCs | PDX1 | activin A, β-mercaptoethanol, N2, B27, bFGF, nicotinamide | Expression of β-cells markers, insulin, and C-peptide secretion |
| (Xu et al. 2017) | human umbilical cord MSCs | PDX1-PAX4 | B27 | Acquisition of β-cells phenotype, expression of endocrine markers, insulin secretion |
| (Gao et al. 2018) | human adipose tissue-derived MSCs | PDX1 | N/A | Insulin secretion |