Chemoattractant and Stem Cells in the Regeneration of Intervertebral Discs

Background and Aim: Having exploited an organ culture model of inducedIVD degeneration, we have reported that the human mesenchymal stemcells (MSCs) could migrate via the endplate of a bovine disc. In addition,the degenerative disc conditioned medium could significantly upregulatethe expression of certain chemokine receptors in the MSCs cultured,which indicate the responsiveness of these cells to the degenerativeenvironment. We have also looked at the likelihood of MSC recruitmentin the disc in vivo using a mouse tail model of induced disc degeneration,even though only a limited number of bone-marrow cells were used inthe disc.Methods: The migration of MSCs through the endplate was furtherinvestigated by injecting the chemokine SDF1 into the cavity of a partiallynucleotomized disc in organ culture. Having used a hyaluronan-basedthermoreversible injectable hydrogel, the SDF1 was delivered to supportthe disc cell growth, matrix production and MSC differentiation towardsthe disc-like phenotype.Results: The SDF1-releasing hydrogel was found to significantly increasethe MSC recruitment to the disc, indicating the potential of a chemokinedelivery system to accelerate cell homing. The proteomic profile of theconditioned medium of an IVD maintained under induced degenerativesettings was analyzed in order to identify disc-derived chemotacticfactors. Proteomic analysis demonstrated that the two main chemotacticfactors, CL5/RANTES and CXCL6, could be secreted by the degenerativedisc. The histological sections of bovine and human degenerative discsconfirmed the presence of CCL5/RANTES and its receptors, indicatingtheir key role in cell recruitment.Conclusion: Clear evidence clarifies that the homing of endogenousregenerative progenitor cells might occur in the disc, which could beamplified by the chemoattractant delivery system. Besides, some recentstudies have shown the presence of progenitor cells at different locationsin healthy and degenerative IVDs. Take all, mobilization, augmentationand activation of these endogenous progenitor cell populations validatethem as attractive targets for future regenerative approaches.

کلیدواژه ها:

Stem cell ، Chemoattractants ، Bioreactor ، Hydrogels