Neural stimulation for autoimmune diseases has been successfully documented. Setpoint Medical is a medical company in Valencia, CA, which as of Sept 8 2015 has raised $43 MM in developing a neurostimulator to dampen inflammation in IBD and RA. This neurostimulator targets stimulating the vagus nerve with resultant increase in systemic anti-inflammatory cytokines.
Electrical stimulation enhances cell migration and integrative repair in the meninscus, as shown by Vunjak-Novakovic etal (1) in 2013. That paper cites that electrical signals have been applied toward the repair of articular tissues in the laboratory and clinical settings for over 70 years. Vunjak-Novakovic’s group was able to show an increased expression of the adenosine A2b receptor in meniscus cells after stimulation. After meniscus injury, elevated levels of IL-1 and TNF-a act to increase the production of nitric oxide (NO), prostaglandin E2 (PGE2) to mediate and exacerbate inflammation. The paper notes that “questions remain as to how electrical signals influence cells and propagate their effects”. But also that ”adenosine receptors have been implicated in the electrotransduction of pulsed electromagnetic fields in cartilage”. Stimulation of the high affinity A2a and low affinity A2b adenosine receptor result in adenosine receptors resulted in elevated cAMP (2) and subsequent activation of anti-inflammatory pathways via protein kinase A and EPAC, which in turn result in the suppression of NO and PGE2 (3) and downstream feedback inhibition of TNF-a and IL1-B (4).
The role of inflammation in animal models for Type 1 diabetes is well documented. Adenosine signaling promotes regeneration of pancreatic Beta cells in the Zebrafish as shown by Stainier etal in 2012. (5) This paper shows that the most potent enhancer of B cell regeneration was the adenosine agonist 5’-N-ethylcaroxamindoadenosine (NECA), acting through adenosine receptor A2aa, increased beta cell proliferation in a zebrafish model of diabetes.
During inflammation that intiates T1D, the first cellular responders appear to be macrophages and dendritic cells. CD4+ T cells can be activated by IL-12 released by these first responders. It is thought that this is the first step that recruits the cytotoxic killer T cells to destroy the beta cells. (6) Macrophages and beta cells themselves produce cytokines that escalate neutrophil recruitment to the endocrine pancreas. Macrophages and B cells produce the chemokines CXCa and CXCL2 which recruit CXCR2 expressing neutrophils from the blood to the pancreatic islets. Pancreatic macrophages also secrete IL-1B which induces B cells to secrete CXCR2. (7)
Can we use applied voltage, at physiological pulse levels to stop the first attack on the pancreatic beta cells? Can voltage act to decrease release of cytokines that lure the deadly killer T cells to destroy pancreatic beta cells?
Physiological voltage applied to a co-culture of macrophage and pancreatic beta cells will affect the attack and phagocytosis of beta cells by macrophages.
Co-culture Mouse RAW macrophages with NOD mouse SCID islets.
Using a Grass Stimulator, apply stimulation (proprietary)
View cells using light microscopy to evaluate morphology and macrophage attack and/or phagocytosis of beta cell islets.
Promising results for use of voltage to change the physical interaction of macrophages and beta cells in cultured mouse cells.