173 Hydrogel Matrix Human Stem Cell Based Nucleus Pulposus Intervertebral Disc Regeneration

Abstract

INTRODUCTION: Degenerative disc disease (DDD) is one of the major causes of chronic debilitating low back pain. DDD is characterized by changes in cell populations that result in loss of extracellular matrix (ECM) water holding capacity of the nucleus pulposus. DDD can lead to translation of physiologic loads from the anterior 2/3 to the posterior 1/3 of the spinal column resulting in stress placed on the facets and ligamentum flavum resulting in hypertrophy and canal stenosis. Novel stem cell regenerative therapies could restore the anterior column load via nucleus pulposus regeneration. METHODS: A hydrogel scaffold was created composed of self-assembling polyethylene glycol (PEG) functionalized with acrylate and thiol end groups. The scaffold was impregnated with nucleus pulposus (NP) cells differentiated from human umbilical cord mesenchymal stem cells (MSCs). Impregnated NP-scaffolds were then implanted into an ex vivo rabbit model of DDD and the viability and function of NP cells analyzed. RESULTS: The NP-scaffolds limited leakage and retained the cells in the NP region of the degenerated disc. Both the NP-scaffold and disc environment promoted differentiation of the MSCs into cells types capable of producing the ECM including sulfated glycoaminoglycans at levels higher than MSCs injected into the intervertebral disc. NP-scaffold cells also expressed chrondrogenic markers like SOX9, COL2 and ACAN at higher levels as well as NP markers FOXF1, K19, and Vimentin determined by real-time polymerase chain reaction (PCR) and immunostaining. CONCLUSION: This study demonstrated that a hydrogen scaffold impregnated with NP cells was much more effective at disc regeneration than NP cells alone and can lead to novel therapies for treating DDD.