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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
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