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
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Characterization of neural progenitors cells
研究概览
简要总结
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.
详细描述
- 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients of both sexes with BMI < 25 (normal weight) and BMI > 30 (obese) with or without T2DM with an indication for surgery
排除标准
- •Malignant neoplastic diseases
结局指标
主要结局
Characterization of neural progenitors cells
时间窗: At the end of the epigenetic conversion, the cell cultures are "blocked" and analysed with biochemistry and molecular biology techniques whose protocols and data analysis require 30 days not necessarily continuous
To determine whether neural progenitor cell (NPCs) obtained from dysmetabolic individuals are defective (analysis of degenerative features) when compared with control-derived cells.
Fibroblasts culture characterization
时间窗: About one month to obtain cell cultures from each biopsy. Approximately one month (not necessarily continuous) for in vitro experiments and analyses. Total: 60 days per sample
To determine whether cells from dysmetabolic individuals are defective (in term of proliferation, senescence, cell death) when compared with control-derived cells
Efficiency of fibroblast epigenetic conversion (gene expression analysis)
时间窗: The epigenetic conversion protocol requires 25 days, the analysis of gene expression (qRTPCR) approximately 5 days.
To determine whether cells from dysmetabolic individuals are different in term of epigenetic conversion efficiency when compared with control-derived cells.
次要结局
未报告次要终点