INTRODUCTION: The aim of this study is to examine the effect of inflammatory severity on the ability of mesenchymal stem cells (MSCs) to recover biomechanical and biochemical properties of an injured intervertebral disc (IVD) in vivo. We examined the effect of very early (3 day) vs. later (2 week) administration of MSCs into injured or control IVDs to tease out the potential effect of inflammation on the therapeutic ability of MSCs.
METHODS: Needle puncture (27G) injury was created in two discs of the rat tail, and 2 adjacent discs were uninjured controls. On day 3 (EARLY) or day 14 (LATE) post injury, autologous marrow derived MSCs were injected into a control (CONMSC) and injured (INJMSC) disc. After 14 days post treatment, discs were collected and characterized for compressive dynamic modulus (G*) and GAG content, and compared to the sham and untreated injured dics.
RESULTS: In early group, CONMSC discs had significantly higher GAG content & G* vs. sham, and INJMSC had significantly greater G* vs. sham. In late group, GAG content of CONMSC decreased vs. early, as did G* of INJMSC. G* & GAG content of INJMSC in late group were significantly lower than CONMSC.
DISCUSSION: Our results indicate that the administration of MSCs to injured discs resulted in diminished therapeutic response compared to injection into control discs. INJMSC had comparable results to CONMSCs in the early group, suggesting that the peak levels of cytokine secretion within 4 days of injury do not appear to limit the ability of the MSCs to survive. However, the behavior of MSCs in late group was significantly diminished vs. early group, indicating that timing of the MSC administration can greatly affect the outcome of the therapy. Future studies will explore relationship between mediators of diminished therapy of MSCs in vivo.