Allogeneic mesenchymal stem cell transplanation into the intervertebral disc: effect of serverity of degernation and cell number on regeneratiion

Abstract

INTRODUCTION: Low back pain is associated with the degeneration of intervertebral disc (IVD). The therapeutic effect of autogenic mesenchymal stem cells (MSCs) on disc degeneration has been previously reported. However, autogenic transplantation lacks on-shelf availability in practice and may carry intrinsic factors of degeneration. We hypothesize that allogeneic MSCs can also be effective in IVD rejuvenation and the effect is dependent on cell quantity and degenerative stage. METHODS: Degeneration of IVD at L2/L3 and L4/L5 level was induced by annulus puncture in NZW rabbits. One month after, bone marrow MSCs from Chinchilla rabbits were encapsulated in 0.25% PuraMatrix™ peptide hydrogel at 0.5x104 –1.5x105 cells/10ul and then injected into the degenerated discs, with PBS or hydrogel as controls (6 discs per group). At 1 or 3-month intervals, disc hydration was quantitated by MRI and disc height index was determined from radiographs. The discs were assigned to mild or severe degeneration group base on hydration value at the time of injection. RESULTS: At both mild and severe degenerative stages, allogeneic MSCs were able to arrest the continual loss of total disc hydration at one month post-injection. With the minimal quantity of MSCs, discs of mild group but not the severe group can regain hydration at 3 month post-injection, accompanied by maintenance of maximum hydration and disc height index. Increase in MSCs injection quantity did not result in arrest of degeneration in either degenerative stage. DISCUSSION: Allogeneic MSCs can effectively arrest or even reverse rabbit disc degeneration. For the same cell quantity, the regeneration effect of MSCs is more prominent at mild than severe degenerative stage. A low quantity of MSCs ( 5000 cells) suffices for provoking the regenerative effect while overdose of cells can be detrimental. Self-assembling peptide hydrogel can facilitate the establishment of a hydrophilic core and to resist disc height collapse.