Review Article

Efficiency of Stem Cell (SC) Differentiation into Insulin-Producing Cells for Treating Diabetes: a Systematic Review

Table 1

Overview of in vitro differentiation efficacy of SCs into IPC.

Cell sourceIntervention (s)OutcomeAuthor (year)

BM-MSCsPdx-1 transfectionThe results demonstrated that Pdx-1 could improve differentiation efficacy of BMSCs to IPC and increase gene expression.Sun et al. [9]
BM-MSCsFibronectin and lamininThe data showed pancreatic differentiation enhancement.Lin et al. [31]
BM-MSCsPancreatic tissue extractPancreatic tissue extract effectively promoted differentiation efficiency and maturity of IPCs.Xie et al. [20]
BM-MSCsExendine-4Results demonstrated EX-4 significant increase in differentiation of IPCs from RAT-BM-MSCs.Dehbashi-Nejad et al. (2014)
BM-MSCsNonadherent stateNonadherent induction greatly improved the differentiation efficiency of BMSCs towards IPCs.Zhang et al. [35]
BM-MSCsFibrin glue (FG), Pdx-1, Glut-2, (3D culture)FG scaffold enhanced the differentiation of IPCs from rat BM-MSCs.Khorsandi et al. [24]
WJ-MSCsExendin-4Incorporating exendin-4 significantly improved the differentiation outcome of WJ-MSCs into IPCs.Kassem et al. [23]
WJ-MSCsDecellularized liver scaffolds (3D culture)3D scaffold improved differentiation of WJMSCs to IPCs.Zhou et al. [38]
UC-MSCsLaminin 411Laminin 411 significantly enhanced differentiation efficiency of IPCs from MSCs.Qu et al. [32]
UC-MSCsHanging drops (3D culture)Differentiation of hUCMs into insulin-secreting cells was more efficient in 3D culture than 2D culture.Seyedi et al. [34]
UC-MSCsFibrin scaffoldCells in fibrin scaffold 3D culture system were much more efficient than those in 2D conventional culture system.Seyedi et al. [39]
UC-MSCsPAX4 and PDX1PAX4 promotes the PDX1-induced differentiation of MSCs into functional β-cells.Xu et al. [16]
AD-MSCsCollagen/hyaluronic acid (Col/HA) scaffold (3D culture), PDX1The results showed that COL/HA scaffold enhanced the differentiation of IPCs from rat AMSCs.Khorsandi et al. [36, 37]
AD-MSCsExendine-4EX-4 significantly enhanced the differentiation of ADMSCs into IPCs.Khorsandi et al. [24]
iPMSCsConophyllineData showed that conophylline promoted the iPMSC differentiation into islet-like clusters.Zhang et al. [35]
iPSCPDX-1 and NKX6.1 transfectionEfficiency of differentiation of iPSC to IPC increased by concurrent expression of PDX1 and NKX6.1.Walczak et al. [14]
iPSCsTestosteroneThe addition of testosterone into routine differentiation formula for pancreatic beta cells increased differentiation efficiency from 12% to 35%.Liu et al. [26]
PSCsSequential modulation of multiple signaling pathwaysThe stem cell-derived beta cells expressed markers found in mature beta cells and secreted quantities of insulin comparable to adult beta cells in response to multiple sequential glucose challenges in vitro.Pagliuca et al. [18]
PSCsCoculture with mature isletsResults suggested that mature islet cells could increase the differentiation efficiency of PE cells into mature IPCs via paracrine effects.Oh et al. [28]
ESCsActivin AResults indicated that the hES cell-derived insulin-expressing cells contained many cell components critical to β-cell function.D’Amour et al. [19]
ESCsPax4 nucleofectionData demonstrated that pax4 increased differentiation of ESCs.Lin et al. (2007)
ESCsPax4 overexpressionResults showed that overexpression of Pax4 enhanced generation of cells resembling pancreatic β-cells.Liew et al. [12]
ESCsExtracellular matrixResults showed that matrigel-coated plates increased the differentiation efficacy of ESCs into IPCs (higher expression insulin I, insulin II, Slc2a2, and more insulin secretion).Farrokhi et al. [30]
ESCsExendin-4 transfectionExendin-4 improved the efficiency of ESC differentiation toward the beta cell phenotype.Li et al. [8]
ESCsNgn3 and Pdx1 overexpressionThis combination dramatically increased the differentiation efficacy.Kubo et al. [13]
ESCsCoculture with endothelial cellsResults demonstrated that differentiation of ESCs to insulin-producing cells enhanced by coculture with ECs.Talavera et al. [27]
ESCsPdx1, MafA with either Ngn3 or NeuroD overexpressionTreatment with ESCs promoted differentiation of ES cells into insulin-secreting cells.Xu et al. [10]
hESCsUsing a combination of reagents, including an ALK5 inhibitor, BMP receptor inhibitor, and thyroid hormone (T3)The results showed that highly differentiated cells displayed certain key characteristics of mature beta cells.Rezania et al. [17]
ESCsCollagen type 1Collagen I induced more rapid and consistent differentiation of stem cells to definitive endoderm.Rasmussen et al. [33]
ESCsResveratrolRSV treatment enhanced efficient differentiation of hESCs into β-cell-like cells.Pezzolla et al. [25]
ESCsCoculture with mouse pancreatic isletsResults demonstrated higher differentiation efficiency in the coculture group.Yilmaz et al. [29]
Pancreatic islet-derived mesenchymal stem cellsMafA, Pax4, and Ngn3 transfectionCotransfection of these factors improved differentiation efficiency of the stem cells into insulin-secreting cells.Aciksari et al. [15]

Bone marrow mesenchymal stem cells (BM-MSCs); umbilical cord mesenchymal stem cell (UC-MSC); mesenchymal stem cells isolated from Wharton’s jelly of umbilical cord (WJ-MSCs); adipose-derived mesenchymal stem cell (AD-MSC); embryonic stem cells (ESCs); induced pluripotent stem cells (iPSCs); immortalized pancreatic mesenchymal stem cells (iPMSCs); pluripotent stem cells (PSCs).