Indirect Co-culture of Human Adipose-Derived Stem Cells and Nucleus Pulposus Cells for Intervertebral Disc Regeneration Using Peptide-Conjugated Hydrogels
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Intervertebral disc degeneration (IVDD) is a main cause of chronic low back pain, which results in significant economic loss to society and compromised life quality of patients. Traditional treatments of IVDD include surgical procedures, such as discectomy, and spinal fusion. However, these methods cannot preserve the biological or biomechanical functions of the intervertebral disc (IVD). Moreover, they decrease the mobility of the associated spinal motion segment and increase the load and stress on contiguous discs. Currently, artificial IVD replacements have gained interest. Although these implants are capable of preserving disc motion and disc height, they are unable to sustain compressive forces applied on the IVD due to their lack of elasticity. Therefore, there is a great need for an alternative therapeutic strategy for the treatment of IVDD. For mild or early stages of IVDD, regeneration by injecting pre-differentiated adipose-derived stem cells (ASCs) into the nucleus pulposus (NP) has been considered. This study aimed to investigate whether NP cells could direct human adipose-derived stem cells (hASCs) to differentiate into an NP cell phenotype. These cells could then serve as an alternative cell source for the treatment of intervertebral disc degeneration in the clinical setting. Interactions of ASCs and NP cells were studied via an indirect co-culture system using N-cadherin conjugated hyaluronic acid (HA) embedded within calcium alginate gels as scaffolds by evaluating the changing profiles of extracellular matrix (ECM) components, including glycosaminoglycans (GAGs) and type II collagen. NP cells showed the potential ability to induce hASC differentiation in terms of enhanced ECM production, such as collagen and GAG in an indirect co-culture system.