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International Journal of Bioprinting Bioprinting of β-islet-like constructs
Figure 1. Cell types and pancreas genesis. (A) Several cell types contribute to the morphology of pancreatic islets. (B) The endocrine pancreatic progenitor
cells and main transcription factors associated with the principal phases of β-cell genesis. Abbreviations: Pdx1, pancreatic and duodenal homeobox1; Pt-
f1a, pancreas-specific transcription factor1a, SOX9, sex determine region Y (SRY)-box9; Ngn3, neurogenin3; Arx, Aristaless-related homeobox X-linked;
Pax4, paired box 4; MafA, maturation factor A; GLP1, glucagon-like peptide1; PC1/3, proconvertase 1/3. (C) Schematic view of cell sources in bioartificial
pancreatic islets. Abbreviations: ESCs, embryonic stem cells; BM-MSC, bone marrow mesenchymal stem cells; AD-MSC, adipose-derived mesenchymal
stem cells; CB-MSC, cord blood mesenchymal stem cell; iPSC, induced pluripotent stem cells; OKT4, octamer binding transcription factor 4; SOX2,
SRY-related high mobility group box protein 2; KLF4, Kruppel-like factor 4; MYC, myelocytomatosis viral oncogene.
proliferation, differentiation, and apoptosis [25,26] . ECM common high molecular weight component in the ECM of
components and ECM-associated growth factors are human tissues . Islet cell matrix characterizations indicate
[30]
concerned with β-cell survival, proliferation, and insulin interactions between FN and integrins . FN improves
[32]
secretion in mature normal pancreatic islets. Besides viability and proliferation in rat islets and reduces apoptosis
type IV and VI collagens, other ECM components in the in MIN6 β-cell line [29,32] . GAGs are linear repeating units
pancreatic islets are laminins, FN, GAGs, and heparan of disaccharides, comprising one hexosamine and uronic
sulfate proteoglycans (HSPGs) [8,27] . Type IV collagen acid . Predominant GAGs in pancreatic ECM are
[33]
comprises a significant portion of ECM in the vascular hyaluronic acid (HA) and HSPG. HSPGs have protective
basement membrane of the pancreatic islets [8,28] . Collagens activity for β-cells versus reactive oxygen and other
promote the maintenance of isolated primary islets and oxidant elements that induce apoptosis [33,34] . Reducing
β-cell lines [28–30] . Laminins increase the survival of isolated or eliminating proteoglycans reduces β-cell proliferation
primary islets and β-cell lines in mice and promote the and increases their apoptosis [35,36] . Studies in human islets
proliferation of primary islets and postnatally β-cell lines have shown that reduced synthesis of GAGs generally
in humans [29,31] . FN, which has a glycoprotein structure, is a reduces islet amyloid formation . β-cells link to ECM via
[35]
Volume 9 Issue 2 (2023) 258 http://doi.org/10.18063/ijb.v9i2.665

