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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05755321
• Other study ID #: Prot 9693/18 ID:1910
• Status: Active, not recruiting
• Start date: January 1, 2020
• Est. completion date: May 14, 2023

Study information

• Verified date: February 2023
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

• 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: May 14, 2023
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Diabetes Mellitus
• Diabetes Mellitus Type 2 in Nonobese
• Diabetes Mellitus Type 2 in Obese
• Diabetes Mellitus, Type 2
• Metabolic Diseases
• Metabolism Disorder
• Obesity

Intervention

Other:
• Skin biopsy
Skin biopsy performed during surgery.

Locations

Country	Name	City	State
Italy	Mingrone Geltrude	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fibroblasts culture characterization	To determine whether cells from dysmetabolic individuals are defective (in term of proliferation, senescence, cell death) when compared with control-derived cells	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
Primary	Efficiency of fibroblast epigenetic conversion (gene expression analysis)	To determine whether cells from dysmetabolic individuals are different in term of epigenetic conversion efficiency when compared with control-derived cells.	The epigenetic conversion protocol requires 25 days, the analysis of gene expression (qRTPCR) approximately 5 days.
Primary	Characterization of neural progenitors cells	To determine whether neural progenitor cell (NPCs) obtained from dysmetabolic individuals are defective (analysis of degenerative features) when compared with control-derived cells.	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