Degenerative Disc Disease
Conditions
Keywords
inflammation, degeneration, spine unit, intervertebral disc, mesenchymal stem cell
Brief summary
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.
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
Interventions
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.
Sponsors
I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of MSC-derived secretome | 30 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of patient-specific degenerative features | 30 months | Identification of circulating degenerative features related to ageing and inflammation in patients affected by Degenerative Disc Disease (DDD) correlating with tissue degeneration. |
| Development of an organotypic spine unit model | 30 months | Determination of success or failure in the development of spine unit models for each enrolled patient from which cell isolation has been successful. |
Countries
Italy
Outcome results
None listed