Role of Hematopoietic Stem Cells in Inflammation of the Pancreas during Diabetes Mellitus

Abstract

The model of streptozotocin-induced diabetes mellitus in C57Bl/6 mice was employed to study the role of precursors of insulin-producing β-cells, hematopoietic stem cells, and progenitor hematopoietic cells in inflammation. In addition to provoking hyperglycemia, streptozotocin elevated serum levels of IL-1β and hyaluronic acid, induced edema in the pancreatic insular tissue and its infiltration by inflammatory cells (neutrophils, lymphocytes, and macrophages) and fibroblasts. Inflammation in pancreatic islets was accompanied by necrotic processes and decreasing counts of multipotent progenitor β-cells (CD45(-), TER119(-), c-kit-1(-), and Flk-1(-)), oligopotent progenitor β-cells (CD45(-), TER119(-), CD133(+), and CD49f(low)), and insulinproducing β-cells (Pdx1(+)). Pancreatic infl ammation was preceded by elevation of the number of short-term hematopoietic stem cells (Lin-Sca-1(+)c-kit(+)CD34(+)) relative to long-term cells (Lin(-)Sca-1(+)c-kit(+)CD34(-)) in the bone marrow as well as recruitment of hematopoietic stem and progenitor cells into circulation. Transplantation of bone marrow hematopoietic stem and progenitor cells from diabetic C57Bl/6 donor mice to recipient CBA mice with 5-fluorouracilinduced leukopenia accelerated regeneration of granulocytopoiesis in recipient mice.

Anti-inflammatory and antioxidant potential capacities of AD-MSCs and BM-MSCs in suppressing pancreatic β-cells auto-immunity and apoptosis in rats with T1DM induced model

“…However, oxidative stress injury and elevated ROS and MDA production were recognized as the major etiological factor in the development of diabetes; which might be a reflection of the decreased antioxidant capability of the defensive systems and/or glucose oxidation (Aminzadeh et al, 2020;Kodidela et al, 2020). Moreover, Dygai et al (2016); Bathina et al (2017) stated that, in addition to provoking hyperglycemia in diabetic rats, STZ could enhance increased oxidative stress and proinflammatory cytokines; such as CRP, TNF-α, IFN-γ, hyaluronic acid, IL1-β, and IL-6; which are positively correlated with measures of insulin deficiency; through inducing edema in the pancreatic insular tissue and its infiltration by inflammatory cells and fibroblasts.…”

Pancreaticline Cell Differentiation of Bone Marrow Mesenchymal Stromal Cells in Acellular Pancreatic Scaffolds

“…Both CK7 and Flk-1 are localized normally in the pancreatic duct structures in the adult pancreas and contribute to the formation of the large intralobular, the interlobular, and the main duct [44]. Coupled with CK7, Flk-1 functions as the receptor of vascular endothelial growth factor, which is associated with the endothelial layer of the vasculature [45,46].These two markers are known to be expressed during pancreatic morphogenesis in the fetus [47]. C-peptide is expressed in pancreatic endocrine cells which indicate β-cells function [48].…”

Pancreatic line Cell Differentiation of bone marrow Mesenchymal Stromal Cells in Acellular Pancreatic Scaffolds

“…Both CK7 and Flk-1 are localized normally in the pancreatic duct structures in the adult pancreas and contribute to the formation of the large intralobular, the interlobular, and the main duct [41]. Coupled with CK7, Flk-1 functions as the receptor of vascular endothelial growth factor, which is associated with the endothelial layer of the vasculature [42,43].These two markers are known to be expressed during pancreatic morphogenesis in the fetus [44]. C-peptide is expressed in pancreatic endocrine cells which indicate β-cells function [45].…”