The role of stem and progenitor cells in the regeneration of the pancreas and testes in metabolic disorders

Abstract

The aim of this research was to investigate the regenerative potential of stem and progenitor cells derived from the pancreas and testes in metabolic disorders.Materials and methods. The experiments were performing on C57Bl/6 mice. Metabolic disorders (MD) were modeling by streptozotocin and fat diet. Morphological methods were used to assess morphopathological changes in the pancreas and testicular tissue and fertility. We investigated the insulin expression in the islets of Langerhans, CD16 in testes by immunohistochemical methods. We evaluated the blood lipids, level of glucose, inflammatory mediators, testosterone and a glucose-dependent insulinotropic polypeptide levels in biological samples by biochemical methods and ELISA. We used cytometric methods to study the surface markers of stem and progenitor cells, culture methods and transplantation test to investigate the regenerative potential of stem and progenitor cells.Results. After streptozotocin injection and fatty diet we observed the metabolic imbalance of lipids, testosterone, glucose and insulin resistance in C57BL/6 male mice. The inflammation, type 2 diabetes, asthenoand oligozoospermia were developed and the fertility index was decreased after the metabolic disorders. We observed the increase of oligopotent β-cell precursors (CD45- TER119- CD133+CD49flow) and precursors of hemangiogenesis (CD45- TER119- cKit-1+Flk-1+) count in the pancreas, spermatogonial stem cells (CD117- CD90+ and CD117+CD90+) and precursors of hemangiogenesis (CD45- TER119- cKit-1+Flk-1+) in the testes in MD. Stem and progenitor cells had a high clonal activity and self-renewal capacity, the ability to differentiate into mature cells in vitro, the effective engrafment in injured tissue.Conclusions. In experiments in vitro and in vivo we detected a high regenerative potential of precursors of hemangiogenesis and insulin-producing β-cells, spermatogonial stem cells of C57BL/6 male mice with metabolic disorders. Low rates of regeneration of the microvasculature, insulin-producing β-cells and germ cells in metabolic disorders are associated with the inhibitory effect of diabetic factors and inflammation on stem and progenitor cells.

Keywords

• метаболические нарушения
• воспаление
• диабет
• гипогонадизм
• сперматогониальные стволовые клетки
• предшественники гемангиогенеза
• предшественники β-клеток
• регенерация