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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

