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

Bull Exp Biol Med. 2016 Feb;160(4):474-9. doi: 10.1007/s10517-016-3200-1. Epub 2016 Feb 23.

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.

Keywords: IL-1β; diabetic inflammation; hematopoietic stem cells; hyaluronic acid; multipotent precursors of β-cells.

MeSH terms

  • Animals
  • Bone Marrow Cells
  • Cell Differentiation
  • Cell- and Tissue-Based Therapy / methods*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Fluorouracil
  • Granulocytes / cytology
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / immunology*
  • Hyaluronic Acid / blood
  • Hyperglycemia / chemically induced
  • Hyperglycemia / therapy*
  • Inflammation / therapy
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / pathology
  • Interleukin-1beta / blood
  • Leukopenia / chemically induced
  • Leukopenia / immunology
  • Leukopenia / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Streptozocin

Substances

  • IL1B protein, mouse
  • Interleukin-1beta
  • Streptozocin
  • Hyaluronic Acid
  • Fluorouracil