The effect of doxycycline and collagenase A on the differentiation of mesenchymal stem cells towards a nucleus pulposus phenotype

Intervertebral disc (IVD) degeneration costs the healthcare system billions of dollars annually and leads to reduced quality of life. Current treatments are invasive and primarily focus on symptom relief rather than repair. This study aimed to facilitate the development of an injectable therapy using chondrogenically differentiated mesenchymal stem cells (MSCs) in the absence of collagen II deposition. Briefly, pelleted MSCs were cultivated in chondrogenic medium and were supplemented with collagenase A or doxycycline in order to inhibit collagen assembly. Results indicated that collagenase A and doxycycline treatment had no negative effects on DNA or proteoglycan content. Collagenase A at all concentrations affected collagen content, as did doxycycline at low concentrations. Furthermore, preliminary gene expression studies for nucleus pulposus markers showed that collagenase A and doxycycline may have some effect on terminal differentiation of MSCs in chondrogenic medium. Overall, the findings suggest that collagenase A and doxycycline supplementation can be used to inhibit collagen formation, thereby facilitating the further development of an injectable therapy for IVD repair.