Spine Unit Modelling Coupled With hIgh Throughput Analysis (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.

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

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