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International Journal of Bioprinting                                    Bioprinting of β-islet-like constructs



            Table 1. Extracellular matrix (ECM) components and their functions on pancreas islets
             ECM ingredients      Function in tissues              Role in pancreatic islets         References
             Type ΙV and VΙ collagens   Abundant part of ECM in the vascular basement   Promote durability of isolated primary islets and   [26–28]
                                  membrane                         β-cell lines
             Laminins             Heterodimer glycoproteins consisting of three   •  Increase the durability of isolated primary islets   [29,31]
                                  polypeptide chains                 and β-cell lines in mice
                                                                   •  Critical for β-cell expansion and insulin release
                                                                     in humans
             Fibronectins (FNs)   High molecular weight glycoproteins, like colla-  Improve viability and expansion of rat islets and   [29,30,32]
                                  gens, which are a major component of ECM in   reduces apoptosis in MIN6 β-cell line
                                  human tissues
             Glycosaminoglycans   Similar to HA, if alone, and covalently linked to   Associate with β-cell function, involvement in the   [34–36]
             (GAGs)               core proteins to form proteoglycans  ECM of the vascular basement membrane, and
                                                                   amyloid formation
            ECM, extracellular matrix; HA, hyaluronic acid.
            transmembrane integrin receptors. Integrins are necessary   characterized  by  low  insulin  production  by  β-cells  and
            for maintenance and signal transfer in β-cells. Similarly,   requires daily insulin administration. T2D, also called
            integrins cooperate with the access and activity of growth   non-insulin-dependent or adult diabetes, results from
            factor receptors, which are essential for developing the   body cells, low insulin response, or insulin resistance. T1D
            pancreatic islets during the embryogenesis, function, and   is an autoimmune disease, whereas T2D is considered a
                                                                             [43]
                                      [37]
            survival of β-cells until adulthood . There is evidence that   metabolic disease . Although the primary triggers of
            increasing β1 integrins–ECM interactions can promote   the immune system against β-cells are unclear, except for
            survival, proliferation, and protection against anoikis of   environmental  factors  and  some  viral  infections,  a  long
            transplanted islets (Table 1) .                    list of genetic  polymorphisms has been introduced to
                                  [38]
                                                               contain related genes to the susceptibility of T1D. MHC
            2. Pathology of pancreas β-Islets and the          class II genes, insulin gene area, CTLA4 gene, and PTPN22
                                                                                       [44,45]
            unmet medical needs                                gene are the most prominent  . There is evidence that
                                                               innate immune activation causes the activation of antigen-
            Any changes in the pancreatic islets’ environmental   specific lymphocytes (CD8  T cells) that can destroy
                                                                                      +
            balance can alter the normal function of their cells, thereby   β-cells [46,47] . The loss of β-cells and the consequent lack of
            increasing or decreasing the secretion of pancreatic   insulin secretion causes the onset of symptoms of T1D and
            hormones. Common disorders affecting the pancreatic   complications that follow. Diet and lifestyle patterns, early
            islets’ duty are pancreatitis, autoimmunity, tumors, and   prognosis, and appropriate cure to controlling glucose
            trauma . According to the American Cancer Society   balance are essential in reducing diabetic complications.
                  [39]
            statistic, pancreatic tumor accounts for 3% of all cancers and   Several scholars have proposed that immunomodulators,
            8% of all cancer deaths in the United States . Pancreatic   hormone peptides, pancreas transplantations, and
                                               [40]
            tumor is the fourth cause of death among the deadliest   mesenchymal stem cells (MSCs) can effectively control
            malignancies . Most pancreatic cancers are exocrine   and alleviate diabetic involvement. Although pancreatic
                      [40]
            cancers. Pancreatic neuroendocrine tumors (NETs), or   islet  transplantation offers a  promising  approach  to
            islet cell tumors, are less prevalent and meanwhile have a   treating patients with T1D, exogenous insulin remains the
            better prognosis . One classification tumor of the NETs   conventional therapy for these patients. In recent decades,
                         [40]
            is  a  functioning  or  nonfunctioning  tumor.  The  most   several attempts have been made to improve insulin
            common functioning tumor is insulinoma . Insulinoma   delivery to prevent daily injection complications for
                                              [41]
            is the only subtype of islet cell adenoma derived from   diabetic patients. Long-acting insulin, insulin pumps, and
            β-cells and secretes a high level of insulin in the blood and   artificial pancreas can help to some extent. Nevertheless,
            causes hypoglycemia. Patients with nonfunctional tumors   by daily injections or continuous subcutaneous insulin
            are often associated with advanced disease because they do   pumps, exogenous insulin compensates for the shortage
            not show any hormonal changes during early detection .   by  producing  endogenous  insulin  but  does  not  imitate
                                                        [42]
            Diabetes is an autoimmune disease that ensues when   the physiological pancreatic insulin sprinkle convention.
            the pancreas does not deliver adequate insulin or when   Hypoglycemic episodes leading to macrovascular and
            the body cannot react to the existing insulin. Type 1   microvascular complications are life-threatening to
            diabetes (T1D) or insulin-dependent juvenile diabetes is   patients. β-cell replacement strategy, including the entire


            Volume 9 Issue 2 (2023)                        259                     http://doi.org/10.18063/ijb.v9i2.665
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