Synthetic Fibroblasts: Terra Incognita in Cardiac Regeneration

Ischemic heart disease, a major risk factor for myocardial infarction (MI), occurs when the blood vessels supplying oxygen-rich blood to the heart become partially or fully occluded by lipid-rich plaques, resulting in myocardial cell death, remodeling, and scarring. In addition, MI occurs as result of lipid-rich plaque rupture, resulting in thrombosis and vessel occlusion. Cardiac fibroblasts (CFs) and CF-derived growth factors are crucial post-MI in myocardial remodeling. Information regarding the regenerative phenotypes of CFs is scarce; however, regenerative CFs are translationally relevant in myocardial regeneration following MI. The emerging technologies in regenerative cardiology offer cutting-edge translational opportunities, including synthetic cells. In this review, we critically reviewed the current knowledge and the ongoing research efforts on application of synthetic cells for improving cardiac regeneration post-MI. Impact statement Synthetic cells offer tremendous regenerative potential in otherwise deleterious cardiac remodeling postmyocardial infarction. Understanding the role of fibroblasts in cardiac healing and the therapeutic applications of synthetic cells would open a multitude of novel cardiac regenerative approaches. The novel concept of synthetic fibroblasts that emulate native cardiac fibroblasts can provide an effective solution in cardiac healing.