STL utilizes 2D culture models to explore new concepts and test preliminary hypotheses. 3D models such as pellet and hydrogel constructs increase model relevance to mimic IVD conditions. Co-culture hydrogel constructs allow for direct cell-cell interaction while maintaining the ability to control model culture conditions.
Stem cell therapy and engineered Intervertebral Discs have been proposed to to treat IVD degeneration. However, there are caveats with such techniques. Pro-anabolic approaches have been proposed such as viral gene editing, however viral transfections can cause mutagenesis and immune rejection. Our work used novel nanotechnology and engineered vesicles to deliver "healthy" factors into IVD cells on the celluar and tissue level to reprogram disease cells back to a native phenotype.
The immune system plays a vital role in regulating body homeostasis. In times of disease/sickness it can be activated to release a cascade of inflammatory cells and molecules that protect and remodel our body to prevent further damage. The intervertebral disc has an unique avascular enviroment, making it difficult for immune cells to infiltrate this organ. Even so, immune cells have been shown to be present in the disc, however their function remains unknown. Understanding the roles that different immune cells found in the disc have on structure and function of the IVD is vital to developing better treatments for LBP.
The healthy intervertebral disc (IVD) is avascular and aneural, in part due to the inhibitory effects of extracellular matrix components such as Aggrecan. During the progression of IVD degeneration, however, there is a shift in matrix remodeling with a net loss in extracellular matrix components. This matrix breakdown coincides with angiogenesis and neoinnervation into the disc, resulting in discogenic back pain. Although Aggrecan has been shown to inhibit nerve growth, the exact mechanism is still unknown. By examining the inhibitory effects of various components of the extracellular matrix on neurovascular ingrowth, possible therapeutics can be developed.
The Intervertebral Disc (IVD) along with being the largest aneural organ in the human body is the largest avascular organ in the human body as well. This means the IVD's sole source of nutrition is from diffusion through the Cartilaginous End Plates between the IVD-Vertebra interface and the periphery. This lack of nutrition results in low levels of glucose and oxygen and high levels of lactic acid in the center of the IVD. Using this information, we strive to understand how the individual cells of the IVD cope with this unique and harsh environment.
Mechanical load is a large part of the IVD environment and has been shown to induce cell response and differentiation. In order to mimic in vivo conditions, a modular soft tissue bioreactor is used to apply mechanical load to the 3D in vitro models including hygrogel cultures and organ cultures.
End Plate Calcificaiton
The normally avascular, aneural intervertebral disc relies on diffusion of metabolites through the cartilage end plate for nutrition. During disc disease, the cartilage end plate becomes increasingly calcified and loses porosity, making diffusion of nutrients difficult and expediting degeneration. We aim to explore the mechanisms of this calcification process and determine potential therapeutic targets.
In Vivo and Ex-Vivo Models
Translational medicine is enabled by the use of in vivo and ex vivo animal models to study disease pathology and options for treatment. Research on biological occurrences within relevant experimental animal models enables insight into the workings of the human condition. Specifically pertaining to the intervertebral disc, pet dogs are commonly treated by veterinary specialists for painful pathologies not entirely different from those experienced by people. Understanding the function of the canine intervertebral disc can promote translation to human painful disc disease while additionally contributing insight into the veterinary patient population.