From Skin Fibroblasts to Neural Stem Cells to Investigate in Vitro the Impact of Diabetes on Adult Neurogenesis

From Skin to Brain: Epigenetic Conversion of Skin Fibroblasts Into Neural Stem Cells to Investigate the Impact of Diabetes on Adult Neurogenesis and Neuronal Function

Obesity and glucose intolerance or overt diabetes are increasing at an alarming rate in the population, and are bound to become a public health issue and a major cause of disability, loss of independence and high social costs in the near future. A large body of evidence has in recent years highlighted, among the negative effects of overnutrition and glucose dysmetabolism, also an acceleration of cognitive decline and of brain senescence, through cellular (vascular, neuronal, or both) and molecular mechanisms still incompletely clarified. Understanding how overweight and impaired glucose homeostasis negatively affect brain function represents both a major scientific challenge and an avenue to early detection and possibly prevention of this invalidating complication. The aim of this project is to obtain neuronal progenitor-like cells from skin fibroblasts in order to correlate patient-specific metabolism to adult neural stem cell (NSC) and neuronal function in vitro.

• Analysis of skin fibroblasts from normal, obese, lean/diabetic and obese/diabetic individuals and in vitro epigenetic conversion, as revealed by morphological changes, loss of mesenchymal markers and expression of pluripotency genes.
• To re-differentiate patient-derived pluripotent cells into neural progenitor (NP) and to test their proliferative, self-renewal and multilineage differentiation capacity.
• To evaluate neuronal cells derived from patient and control pluripotent cells for a number functional and biochemical parameters (apoptosis/autophagy, mitochondrial potential, reactive oxygen species etc.) relevant to neurodegenerative disorders.

Inclusion Criteria:

• Patients of both sexes with BMI < 25 (normal weight) and BMI > 30 (obese) with or without T2DM with an indication for surgery

Exclusion Criteria:

• Malignant neoplastic diseases