Indicators of cardiovascular homeostatic imbalance:
Homeostatic Imbalance-most disease is seen to be the result of
Cardiovascular disease is the consequence of a complex series of events that begins with one or more homeostatic imbalances initiated by abnormal gene environment interaction(s). Factors or agents that induce biochemical or physical stress/injury can elicit pathophysiological responses that include molecular, cellular, tissue, and/or integrative processes. Accordingly, the responses may be of a systemic, circulating, or local nature. In genetically susceptible individuals, these pathophysiologic responses can result in tissue damage, ultimately leading to impaired tissue function, target organ failure, clinical events, or death.
what is homeostatic imbalance, and what diseases result from it?
Current paradigms for diabetes treatment are inadequate at responding accurately to short term homeostatic imbalances and cannot prevent chronic diabetes-related complications. Predictably, novel approaches to re-establish homeostatic conditions in patients afflicted by type 1 diabetes (T1D) are now under intense investigation. Notably, the ex vivo generation and injection of tolerance-promoting dendritic cells (DCs) is being pursued in clinical trials for applications in T1D. While instructive, exogenously-conditioned cellular-based vaccines for T1D treatment have numerous limitations. Dissemination of exogenously delivered DCs is inefficient, and treatment involves a personalized medicine approach involving the generation of cultured DCs, which amounts to high production and treatment costs that prohibit widespread application. To circumvent these limitations, we are developing a multifunctional, synthetic microparticle-encapsulating vaccine that can be easily administered with simultaneous and continuous delivery using controlled-release materials (poly lactide-co-glycolide) for the in vivo conditioning of DCs and amelioration of T1D. Moreover, these microparticle-based vaccines are engineered to target DCs, and provide both intracellular and extracellular delivery of immunomodulatory agents as well as antigen. Our ultimate goal is to develop a microparticle-based (MP) vaccine capable of reversal of T1D in humans. To date, we have demonstrated (i) the ability of targeted MPs to improve in vivo DC uptake and translocation, (ii) the effect of our non-targeted MP vaccine on bone marrow-derived DC phenotype and downstream effects on allogeneic T cells, and (iii) the efficacy of the non-targeted MP vaccine to prevent diabetes onset in NOD mice. Current investigative work is focused on exposing the cellular mechanisms behind the observed prevention in NOD mice, reversal of type 1 diabetes and, evaluating the safety of this biomaterial formulation in rodent models (at OneVax, LLC), with an eye on full translation of this technology.