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

March 8, 2023 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Observational

Enrollment (Actual)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Roma, Italy, 00188
        • Mingrone Geltrude

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients of both sexes with BMI < 25 (normal weight) and BMI > 30 (obese) with or without T2DM

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
BMI<25 and T2DM
10 Subjects with Body Mass Index (BMI) <25 with Type 2 Diabetes Mellitus (T2DM) of both sex.
Other: Skin biopsy
Skin biopsy performed during surgery.
BMI<25 without T2DM
10 Subjects with Body Mass Index (BMI) <25 without Type 2 Diabetes Mellitus (T2DM) of both sex.
Other: Skin biopsy
Skin biopsy performed during surgery.
BMI>30 and T2DM
10 Subjects with Body Mass Index (BMI) >30 with Type 2 Diabetes Mellitus (T2DM) of both sex.
Other: Skin biopsy
Skin biopsy performed during surgery.
BMI>30 without T2DM
10 Subjects with Body Mass Index (BMI) >30 without Type 2 Diabetes Mellitus (T2DM) of both sex.
Other: Skin biopsy
Skin biopsy performed during surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fibroblasts culture characterization
Time Frame: 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
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
Efficiency of fibroblast epigenetic conversion (gene expression analysis)
Time Frame: 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.
The epigenetic conversion protocol requires 25 days, the analysis of gene expression (qRTPCR) approximately 5 days.
Characterization of neural progenitors cells
Time Frame: 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.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

  • Principal Investigator: geltrude mingrone, Policlinico A. Gemelli IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2020

Primary Completion (Anticipated)

April 30, 2023

Study Completion (Anticipated)

May 14, 2023

Study Registration Dates

First Submitted

February 23, 2023

First Submitted That Met QC Criteria

February 23, 2023

First Posted (Actual)

March 6, 2023

Study Record Updates

Last Update Posted (Estimate)

March 10, 2023

Last Update Submitted That Met QC Criteria

March 8, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Prot 9693/18 ID:1910

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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