Stem cell transplantation increases antioxidant effects in diabetic mice

Area of Science:

• Immunology
• Metabolic Diseases
• Nephrology

Background:

• Intra bone marrow-bone marrow transplantation (IBM-BMT) with thymus transplantation (TT) can reduce graft-versus-host disease (GVHD) and restore T cell function.
• Previous studies indicated improved insulin sensitivity in diabetic mice (db/db) following IBM-BMT+TT.
• Heme oxygenase-1 (HO-1) is an enzyme with antioxidant, antiapoptotic, and immune-modulating effects.

Purpose of the Study:

• To investigate the effect of IBM-BMT+TT on heme oxygenase-1 (HO-1) expression in the kidneys of db/db mice.
• To determine the impact of this treatment on renal function and related molecular pathways.

Main Methods:

• Six-week-old db/db mice with hyperglycemia (>250 mg/dl) underwent IBM-BMT+TT.
• Renal function, metabolic parameters, and molecular markers (HO-1, peNOS, pAKT, iNOS, type IV collagen) were assessed six weeks post-transplantation.

Main Results:

• IBM-BMT+TT treatment led to decreased body weight, blood glucose, and insulin levels, alongside increased plasma adiponectin.
• Kidney analysis revealed upregulated HO-1, phosphorylated endothelial nitric oxide synthase (peNOS), and phosphorylated AKT (pAKT).
• Downregulation of inducible nitric oxide synthase (iNOS) and improved type IV collagen expression were observed, correlating with decreased plasma creatinine.

Conclusions:

• IBM-BMT+TT effectively modulates HO-1, peNOS, and pAKT expression while reducing iNOS levels in the kidneys of db/db mice.
• This molecular modulation is associated with significant improvements in renal function and metabolic parameters in diabetic mice.