Spine Unit Modelling Coupled With hIgh Throughput Analysis (SUIT) (SUIT)

Spine Unit Modelling Coupled With hIgh Throughput Analysis (SUIT): Targeting Degeneration With Cell Secretome

Ageing and inflammation represent two main drivers of DDD, a progressive, chronic condition involving vertebral bone, cartilaginous endplate and intervertebral disc.

In vitro investigation of the DDD-associated processes on single compartments of the spine unit or ex vivo animal models fail in recapitulating the complex spine pathophysiology or suffer from inter-species differences. Given these premises, a human organotypic model of the spine unit would represent a suitable tool to investigate the DDD-related pathways and to screen promising treatments such as MSC-based therapies.

Study Overview

• Status: Recruiting
• Conditions: Degenerative Disc Disease
• Intervention / Treatment: Other: Use of patient-derived biological samples

Detailed Description

The primary aim of this study is to investigate the response of an inflamed organotypic spine unit model, intended as a 3D in vitro representation of an in vivo environment, to the treatment with mesenchymal stem cells (MSC)-derived secretome. In particular to investigate the ability of MSC-derived secretome to modulate genes found to be upregulated or downregulated by the inflammatory stimulation in the spine unit model and bring their expression back to a basal state.

Secondary aims of the study are:

• To identify specific degenerative features related to ageing and inflammation in patients affected by Degenerative Disc Disease (DDD) correlating circulating features and tissue degeneration
• To develop an organotypic spine unit model using patient-derived cells to investigate the response of cells derived from nucleus pulposus (NP), annulus fibrosus (AF) and cartilaginous endplate (CEP) to inflammation

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

Study Locations

• Italy
  • Palermo, Italy, 90127
    • Not yet recruiting
    • Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione
    • Contact: Matteo Bulati, PhD; Phone Number: 0039 0912192496; Email: mbulati@ismett.edu
  • MI
    • Milan, MI, Italy, 20157
      • Recruiting
      • IRCCS Ospedale Galeazzi-Sant'Ambrogio
      • Contact: Matteo Moretti, PhD; Phone Number: 0039 0283502220; Email: matteo.moretti@grupposandonato.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Samples will be collected from Degenerative Disc Disease patients undergoing spine surgery, from patients subjected to surgeries that involve the removal of adipose tissue and from pregnant women within 6 hours from giving birth.

Description

DDD patients:

• Signature of the Informed Consent for the study
• Age 30-60 years (included)
• Pfirrmann grade III-V
• Need to undergo spinal surgery

Subjects for the isolation of adipose-derived MSCs:

• Signature of the Informed Consent for the study
• Age 18-50 (included)
• Need to undergo surgery that involves the removal of adipose tissue

Subjects for the isolation of placenta-derived MSCs:

• Signature of the Informed Consent for the study
• Age 18-50 (included)
• Women who are pregnant or who have not given birth from more than 6 hours

All enrolled subjects:

- Presence of HIV, HBV, HCV or TP infection

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Degenerative Disc Disease patients undergoing spine surgery; Collection of blood. Collection of nucleous pulposus, annulus fibrosus and cartilaginous endplate biopsies that would be considered as waste material after surgery.	Other: Use of patient-derived biological samples; We will use biological samples that are routinely collected as waste material from patients undergoing surgery or from pregnant women giving birth. Peripheral blood will be also collected from patients to conduct virological screening and isolate peripheral blood mononuclear cells.
Subjects undergoing plastic surgery; Collection of adipose tissue that would be considered as waste material after surgery.	Other: Use of patient-derived biological samples; We will use biological samples that are routinely collected as waste material from patients undergoing surgery or from pregnant women giving birth. Peripheral blood will be also collected from patients to conduct virological screening and isolate peripheral blood mononuclear cells.
Pregnant female subjects; Collection of amnion of human term placenta (38-40 weeks of gestation) within 6 hours of birth.	Other: Use of patient-derived biological samples; We will use biological samples that are routinely collected as waste material from patients undergoing surgery or from pregnant women giving birth. Peripheral blood will be also collected from patients to conduct virological screening and isolate peripheral blood mononuclear cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of MSC-derived secretome	Changes in gene expression in response to the treatment of the spine unit model with MSC-derived secretome. If the MSC-derived secretome is effective, genes upregulated or downregulated by inflammatory stimulation are expected to go back to their basal levels when the inflamed model is treated with MSC-derived secretome.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of patient-specific degenerative features	Identification of circulating degenerative features related to ageing and inflammation in patients affected by Degenerative Disc Disease (DDD) correlating with tissue degeneration.	30 months
Development of an organotypic spine unit model	Determination of success or failure in the development of spine unit models for each enrolled patient from which cell isolation has been successful.	30 months

Collaborators and Investigators

• Sponsor: I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: March 28, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 8, 2024

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 1, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: intervertebral disc; inflammation; mesenchymal stem cell; degeneration; spine unit
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Intervertebral Disc Degeneration
• Other Study ID Numbers: SUIT

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