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

详细

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.