Production of Stem Cells for the Generation of Pancreatic Cells

Production Of Induced Pluripotent Stem Cells (iPSCs) For The Generation Of Insulin-Producing β Cells

The goal of this interventional study is to generate induced pluripotent stem cells (iPSCs) from somatic cells and differentiate them into insulin-producing β cells in patients with metabolic and genetic pancreatic diseases and in healthy controls. The main questions it aims to answer are:

Can somatic cells from healthy individuals and patients with diabetes be successfully reprogrammed into iPSCs?

Can these iPSCs be differentiated into functional insulin-producing β cells suitable for studying disease mechanisms and developing cell-based therapies?

Participants will provide a single biological sample (either a 3 mm skin punch biopsy, a blood sample, or a urine sample) collected under sterile conditions. The samples will be used to derive somatic cells, which will then be reprogrammed into iPSCs and differentiated into β cells for laboratory analyses.

Participants will:

Undergo a one-time sample collection (skin biopsy, blood draw, or urine collection) at Ospedale San Raffaele

Receive standard post-procedure care (if applicable)

This research aims to improve understanding of β cell function and dysfunction in diabetes and to advance personalized regenerative therapies for β cell replacement.

Study Overview

• Status: Recruiting
• Conditions: Diabetes
• Intervention / Treatment: Procedure: Biological - skin biopsy, blood draw, or urine collection for iPSC generation

Detailed Description

The goal of this interventional study is to investigate how induced pluripotent stem cells (iPSCs) can be efficiently generated from somatic cells and subsequently differentiated into insulin-producing β cells, with the broader aim of improving the understanding of pancreatic β cell biology and supporting the development of future cell-based therapies for diabetes. The study involves the collection of biological samples from both healthy donors and patients affected by metabolic or genetic disorders that impact pancreatic β cell function, such as type 1 diabetes, type 2 diabetes, Maturity Onset Diabetes of the Young (MODY), Wolfram syndrome, and pancreatogenic diabetes.

The primary objective is to establish a reliable and reproducible protocol for the production of iPSCs from somatic cells obtained from different donor groups and to evaluate their potential to differentiate into functional β cells. By comparing iPSC-derived β cells from patients with those derived from healthy controls, the study aims to identify disease-specific cellular and molecular characteristics that may contribute to β cell dysfunction and diabetes pathogenesis. These findings will serve as a foundation for improving strategies for β cell replacement and regenerative medicine.

Participants enrolled in the study will provide a single biological sample, collected at Ospedale San Raffaele in Milan. Depending on the laboratory's technical requirements and the participant's clinical condition, the sample may consist of a 3 mm skin punch biopsy, a small volume of peripheral blood (up to 20 mL), or a urine sample (up to 300 mL). These procedures are all standard clinical techniques performed under sterile conditions by trained healthcare personnel. The risks associated with the procedures are minimal and limited to mild pain, bruising, or, in the case of skin biopsy, a small scar. Participants will receive post-procedure care instructions and will not be required to attend follow-up visits after the sample collection.

Once collected, the somatic cells (such as fibroblasts, peripheral blood mononuclear cells, or urine-derived epithelial cells) will be isolated, expanded, and cryopreserved. These cells will then be reprogrammed into iPSCs using a non-integrating RNA-based reprogramming system (StemRNA™ 3rd Gen Reprogramming Kit, Reprocell). The success of the reprogramming process will be assessed by measuring cell viability and the expression of specific pluripotency markers, including SSEA4, OCT4, and NANOG, through flow cytometry. Only iPSC lines that meet predefined quality criteria-viability above 60% and pluripotency marker expression above 80%-will be considered successful and preserved for further use.

Subsequently, the established iPSC lines will be differentiated into insulin-producing β cells through a stepwise process that mimics pancreatic development. The resulting β-like cells will be analyzed for their ability to produce and secrete insulin in response to glucose stimulation, as well as for other molecular and functional properties. The comparison between β cells derived from healthy donors and those from patients with different forms of diabetes will help elucidate the mechanisms underlying β cell dysfunction and loss in these diseases.

The study will include up to 100 participants, both male and female, aged between 12 and 70 years. At least 30% of participants will be healthy controls, while the remaining will represent patients with various types of pancreatic dysfunction. This approach allows the generation of a diverse biobank of patient-specific iPSC lines, which can be used not only for this study but also for future research projects approved by the Ethics Committee. The total duration of the study is estimated at 10 years, reflecting the long-term nature of iPSC generation, differentiation, and characterization.

Although there are no direct medical benefits for participants, the potential societal benefits of this study are significant. The generation of patient-specific iPSCs provides a powerful platform for studying the pathophysiology of diabetes in vitro, enabling the identification of disease mechanisms and testing of new therapeutic strategies in a personalized way. These cells can serve as models to evaluate how genetic background, environmental factors, and disease states affect β cell development and function. In the long term, this research could contribute to the development of advanced regenerative and transplantation-based treatments for diabetes, potentially reducing or eliminating the need for exogenous insulin therapy.

In summary, this study represents an important step toward bridging fundamental stem cell biology with translational applications in diabetes research. By combining patient-specific iPSC technology with cutting-edge differentiation protocols, it aims to create a resource that not only deepens scientific understanding but also supports the development of innovative and personalized therapies for individuals living with diabetes and related metabolic diseases.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Valeria Sordi, PhD; Phone Number: +390226432643; Email: sordi.valeria@hsr.it

Study Locations

• Italy
  • Milan, Italy, 20132
    • Recruiting
    • Diabetes Research Institute
    • Principal Investigator: Lorenzo Piemonti, MD
    • Contact: Valeria Sordi, PhD; Phone Number: +390226432643; Email: sordi.valeria@hsr.it
    • Principal Investigator: Valeria Sordi, PhD
    • Principal Investigator: Graziano Barera, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Age between 12 and 70 years.

Ability and willingness to provide informed consent (or assent with parental consent for minors).

Group 1: Individuals diagnosed with pancreatic β cell dysfunction, including but not limited to:

Type 1 Diabetes

Type 2 Diabetes

Maturity Onset Diabetes of the Young (MODY)

Wolfram Syndrome

Pancreatogenic Diabetes

Group 2: Healthy control donors without pancreatic β cell dysfunction.

Pregnant or breastfeeding women may be included if they meet the inclusion criteria.

Exclusion Criteria:

Age below 12 or above 70 years.

Health condition too compromised to allow safe tissue collection (e.g., acute hypoglycemia <70 mg/dL or hyperglycemia >140 mg/dL at sampling).

Inability or unwillingness to provide informed consent/assent.

Active malignancy or current cancer treatment.

Known infection with HIV, Hepatitis B, or Hepatitis C.

Use of medications that may interfere with iPSC generation (e.g., high-dose corticosteroids, immunomodulators), unless approved by investigators.

For participants undergoing skin biopsy: bleeding disorders, local skin infection, allergy to anesthetics, or use of anticoagulants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Biospecimen Collection for iPSC Generation and β Cell Differentiation; All participants will provide a single biological sample (skin biopsy, blood draw, or urine collection) for isolation of somatic cells. These cells will be reprogrammed into induced pluripotent stem cells (iPSCs) and differentiated into insulin-producing β cells to study pancreatic function and disease mechanisms. No therapeutic intervention is administered.

Procedure: Biological - skin biopsy, blood draw, or urine collection for iPSC generation; This study involves a single, minimally invasive biological sampling to obtain somatic cells for the generation of induced pluripotent stem cells (iPSCs). Each participant will undergo only one procedure: a 3 mm skin punch biopsy under local anesthesia, a peripheral blood draw (up to 20 mL), or a urine collection (up to 300 mL), depending on laboratory needs. Samples will be processed to isolate fibroblasts, blood cells, or urine-derived epithelial cells, which will be reprogrammed into iPSCs using a non-integrating RNA-based system . The resulting iPSCs will be characterized for pluripotency and differentiated into insulin-producing β cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
generation of iPSC	Successful generation of iPSCs from somatic cells, defined by >80% expression of pluripotency markers (SSEA4, OCT4, NANOG) within 7-60 days after culture establishment.	within 7-60 days after culture establishment

Collaborators and Investigators

• Sponsor: Ospedale San Raffaele

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): February 28, 2035
• Study Completion (Estimated): February 28, 2036

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: diabetes; stem cells, induced pluripotent stem cells
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection; Urine Specimen Collection
• Other Study ID Numbers: iBETA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No