Review Article

Stem Cells as a Tool to Improve Outcomes of Islet Transplantation

Table 1

Described roles of stem cells in islet transplantation.

Stem cellFunctionMechanism

Mesenchymal stem cellsImmunomodulationDecreased activation and proliferation of T cells, dendritic cells, and NK cells, thereby decreasing secretion of inflammatory cytokines including interferon gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and monocyte chemoattractant protein-1 [3136]
Induction of regulatory T cell activation and IL-10 production [35, 37, 38]
Modulation of neutrophil and B cell function and differentiation [35, 37]
Establishment of graft vascular networkSecretion of angiogenic paracrine factors VEGF, IL-6, IL-8, HGF, PDGF, and TGF-β [3944]
Secretion of matrix metalloproteinases [31, 45]
AntiapoptoticSecretion of paracrine factors including HGF, IL-6, and TGF-β resulting in increased expression of genes protective against hypoxia [4648]
Improved β cell architectureUnknown [49]
β cell replacementDifferentiation into insulin-producing cells [5054]

Adipose-derived stem cellsEstablishment of graft vascular networkSecretion of angiogenic paracrine factors VEGF, HGF, bFGF, GMCSF, and TGF-β [37, 55, 56]
Differentiation into endothelial cells [57]
AntiapoptoticSecretion of antiapoptotic growth factors, including HGF, GM-CSF, and TGF-β [56]
β cell replacementDifferentiation into insulin producing cells [5860]

Adipose-derived stem cells + endothelial progenitor cellsEstablishment a vascular network within graftsDirect differentiation into vasculature and pericytes [61]
Release of paracrine factors [61]

Neural crest stem cellsImproved graft innervationNeuronal differentiation [62, 63]

Human embryonic stem cellsβ cell replacementDifferentiation into insulin producing cells [6472]

Induced pluripotent stem cellsβ cell replacementDifferentiation into insulin producing cells [7375]