Ion Therapy: A Novel Strategy for Acute Myocardial Infarction

Abstract

Although numerous therapies are widely applied clinically and stem cells and/or biomaterial based in situ implantations have achieved some effects, few of these have observed robust myocardial regeneration. The beneficial effects on cardiac function and structure are largely acting through paracrine signaling, which preserve the border‐zone around the infarction, reduce apoptosis, blunt adverse remodeling, and promote angiogenesis. Ionic extracts from biomaterials have been proven to stimulate paracrine effects and promote cell–cell communications. Here, the paracrine stimulatory function of bioactive ions derived from biomaterials is integrated into the clinical concept of administration and proposed “ion therapy” as a novel strategy for myocardial infarction. In vitro, silicon‐ enriched ion extracts significantly increase cardiomyocyte viability and promote cell–cell communications, thus stimulating vascular formation via a paracrine effect under glucose/oxygen deprived conditions. In vivo, by intravenous injection, the bioactive silicon ions act as “diplomats” and promote crosstalk in myocardial cells, stimulate angiogenesis, and improve cardiac function post‐myocardial infarction.

Strontium ions protect hearts against myocardial ischemia/reperfusion injury

“…Myocardial ischemia is an enormous threat to public health and mostly caused by coronary artery thrombosis, which reduces or interrupts blood supply and leads to myocardial cell death (28). Recent studies have shown that intravenous injection of the solution containing Si ions could promote functional recovery and myocardial tissue repair after MI (17). However, it is not enough to only find the effective function of Si ions in the infarcted myocardium repair currently, and one of the key issues for bioactive ion therapy is to find an ion with stronger ability of promoting angiogenesis and cardiomyocyte survival.…”

“…As the Sr ions benefit various types of cells, it is possible that Sr ions could harmonically affect various cardiac cells. Since it is important and essential to the interaction between cells in the cardiac tissue, where blood vessel-forming cells and cardiomyocytes coexist (17), we thus investigated the cell-cell interaction in the presence of Sr ions in relation to the angiogenesis using both direct and indirect coculture models (Fig. 2A).…”

“…In addition, we recently found that the transplantation of a silicate ceramic/polymer composite cardiac patch seeded with activated cardiomyocytes is effective to promote the repair of infarcted myocardial by promoting angiogenesis (16). These beneficial effects are associated with the stimulated angiogenesis and enhanced cardiomyocyte viability by the Si ions released from silicate bioceramics (17). These findings suggest that inorganic biomaterials with angiogenic bioactivity may be used for the soft tissue repair.…”

Regenerative and protective effects of calcium silicate on senescent fibroblasts induced by high glucose

“…During clinical practice, their potential in promoting tissue regeneration was gradually uncovered . Previous studies have revealed that the ions released from bioactive materials, such as silicon ions, exerted the bioactivity and influenced cell behaviors . Calcium silicate (CS), a bioceramic made up of a mixture of Na 2 SiO 3 and Ca(NO 3 ) 2, has been shown to promote wound healing in mice by facilitating revascularization .…”

Bioglass could increase cell membrane fluidity with ion products to develop its bioactivity

“…Even though many medical products of BG have been developed and applied, the biological effect of BG, especially ionic product, has not been fully studied. It has been widely reported that Si plays critical roles in the biological effects of BG as it is the only component with different concentrations between the culture medium containing ion products of BG and the normal cell culture medium 1,8,13,14 . But how Si in solution can produce biological effects remains unclear.…”