Low back pain is the second most common cause of doctor visits and intervertebral disc (IVD) herniation is a direct cause of pain. Lumbar discectomy is the standard of care for herniation, yet this very common procedure has 5-25% complication rates including re-herniation and recurrent back pain at the same level. Discectomy complications cannot be further reduced by optimizing the amount of tissue removed during procedures, but instead discectomies require a reparative component to greatly reduce complications. This parent project develops, optimizes and validates biomaterials that seal the annulus fibrosus (AF) and restores nucleus pulposus (NP) swelling following discectomy procedures. Surprisingly, little is known about how aging changes the capacity of annulus fibrosus (AF) cells to promote healing, and no regenerative AF healing models exist. This supplement project investigates the regenerative potential of neonatal IVDs as a way of identifying cellular and molecular repair mechanisms that are lacking in adults to help inform novel IVD repair strategies. This is a highly significant problem since adult human IVDs do not typically heal following AF rupture or herniation. The neonatal mouse is an exciting model of mammalian regeneration for several tissues, yet the regenerative capacity of the neonatal IVD has not been investigated. A regenerative AF healing model could provide a substantial benefit of mapping out successful repair strategies in the IVD with which to mimic and may also help identify important sources of cells and chemokines. The hypothesis is that the neonatal AF is capable of regenerative healing while adult AF repair responses are impaired, resulting in a shift from regenerative healing in neonatal mice to fibrotic healing in adult mice.
Aim 1 will develop a regenerative model of IVD healing in neonatal mice.
Aim 2 will determine the cells involved in AF repair and their phenotype in neonatal and adult mice, with a primary focus on intrinsic IVD cells and a secondary focus on inflammatory cells and transient repair cells. Ms. Olivia Torre is an outstanding PhD candidate from an underrepresented group with a strong commitment to become a principal investigator in an academic environment. This phased supplement is highly candidate focused. The pre-doctoral phase will retain Ms. Torre to complete her PhD studies with additional research and training experiences that allow her to develop new and advanced technical skills, and advance her pathway to independence. The post-doctoral will allow Ms. Torre to pursue highly competitive post-doctoral experiences by identifying a post-doctoral training lab (separate from the PhD mentor), develop pilot data, and submit an F32 or K99/R00 proposal in order to accelerate her advancement towards independent scientist.
This diversity supplement project develops a neonatal mouse model of regenerative healing in intervertebral discs and identifies important cells and molecular factors in injury and repair in neonatal and adult annulus fibrosus tissues. This novel model of regenerative intervertebral disc healing can be used to probe repair mechanisms that are lacking in adults and may help identify innovative strategies for improved intervertebral disc repair to reduce the incidence of back pain. This phased supplement will retain Ms. Olivia Torre, an excellent PhD candidate from an underrepresented group with outstanding potential to develop into an independent scientist, as a pre-doctoral candidate to allow her to complete her PhD studies and then pursue post-doctoral training in order to identify a new mentor, generate data for an F32/K99, and accelerate her pathway towards independence.
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