Chemical Engineering of Cell Therapy for Heart Diseases

Abstract

Cardiovascular disease (CVD) is a major health problem worldwide. Since adult cardiomyocytes irreversibly withdraw from the cell cycle soon after birth, it is hard for cardiac cells to proliferate and regenerate after myocardial injury, such as that caused myocardial infarction (MI). Live cellbased therapies, which we term as first generation of therapeutic strategies, have been widely used for the treatment of many diseases, including CVD. However, cellular approaches have the problems of poor retention of the transplanted cells and the significant entrapment of the cells in the lungs when delivered intravenously. Another big problem is the low storage/shipping stability of live cells, which limits the manufacturability of living cell products. The field of chemical engineering focuses on designing large-scale processes to convert chemicals, raw materials, living cells, microorganisms, and energy into useful forms and products. By definition, chemical engineers conceive and design processes to produce, transform, and transport materials. This matches the direction that cell therapies are heading toward: "produce", from live cells to synthetic artificial cells; "transform", from bare cells to cell/matrix/factor combinations; and "transport". from simple systemic injections to targeted delivery. Thus, we hereby introduce the "chemical engineering of cell therapies" as a concept.

Targeted anti–IL-1β platelet microparticles for cardiac detoxing and repair

“…Acute myocardial infarctions (AMIs), principally caused by the occlusion of a coronary artery, are a major cause of death and disability worldwide (1). MIs induce the reduction of blood flow to heart muscles and result in myocardial necrosis (2,3). The myocardial necrosis triggers a sterile inflammatory response that contributes to adverse left ventricular (LV) remodeling and heart failure (4)(5)(6).…”

Cardiac Cell Therapy for Heart Repair: Should the Cells Be Left Out?

“…There is massive accumulation of acellular therapeutic agents in the liver and kidney after intravenous injection, which reveals rapid clearance and compromised efficacy. To optimize acellular therapy, fabrication and modification of bioengineered secretome, exosomes, antibodies, and nucleic acids with elevated targeting features and prolonged retention have been introduced [ 9 , 146 ].…”

“…Additionally, numerous biomaterials and tissue engineering scaffolds have been fabricated by researchers worldwide to increase the retention and survival rates of transplanted cells. Lastly, entering the new era of cardiac stem cell therapy, stem cells derivatives such as exosomes, secretome, microRNAs, and synthetic stem cell-mimicking materials have been tested [ 8 , 9 ].…”

Recent Development in Therapeutic Cardiac Patches

“…Currently, researchers have discovered that surface modification will largely reduce the tissue adhesion ( 150 ), which may be good candidates for polymer cardiac patches. The biodegradation should also be taken into consideration, as immune rejection will last unless the patches can be degraded after treatment ( 151 ). Such improvement requires the biodegradable of materials themselves, while having little impact on therapeutic period.…”