Stem cell therapy for cardiac repair: benefits and barriers

Abstract

Cardiovascular disease remains the leading cause of death worldwide. Acute ischaemic injury and chronic cardiomyopathies lead to permanent loss of cardiac tissue and ultimately heart failure. Current therapies aim largely to attenuate the pathological remodelling that occurs after injury and to reduce risk factors for cardiovascular disease. Studies in animal models indicate that transplantation of mesenchymal stem cells, bone-marrow-derived haematopoietic stem cells, skeletal myoblasts, or embryonic stem cells has the potential to improve the function of ventricular muscle after ischaemic injury. Clinical trials using primarily bone-marrow-derived cells and skeletal myoblasts have also produced some encouraging results. However, the current experimental evidence suggests that the benefits of cell therapy are modest, the generation of new cardiac tissue is low, and the predominant mechanisms of action of transplanted stem cells involve favourable paracrine effects on injured myocardium. Recent studies show that the adult heart possesses various pools of putative resident stem cells, raising the hope that these cells can be isolated for therapy or manipulated in vivo to improve the healing of cardiac muscle after injury. This article reviews the properties and potential of the various stem cell populations for cardiac repair and regeneration as well as the barriers that might lie ahead.

Stem Cell Therapy for Heart Disease

“…15 Being allogeneic, there are concerns for immunological incompatibility and risk of teratoma formation. 7,16 Secondary to ethical, political and scientific challenges, no heart disease clinical trials used ESC. 16 Animal studies using ESC demonstrated cardiomyocyte differentiation and improved ventricular function.…”

“…7,16 Secondary to ethical, political and scientific challenges, no heart disease clinical trials used ESC. 16 Animal studies using ESC demonstrated cardiomyocyte differentiation and improved ventricular function. 17 These findings spurred development of ESC-like cells by reprogramming adult cells to become undifferentiated pluripotent cells for autologous transplantation, known as induced pluripotent stem cells (iPSC).…”

“…19 BMC contain a mixture of HSC, EPC, MSC, and multipotent adult progenitor cells (MAPC). 2 EPC encompass a cluster of cell types 24 that express CD34 and CD133 markers, 16 as well as growth factors that contribute to angiogenesis. 2 EPC are found in small amounts and are reduced in CAD patients.…”

“…2 EPC are found in small amounts and are reduced in CAD patients. 16 MSC also differentiate into several cell types. 11 MSC and MAPC are considered optimal for allogeneic therapy due to nonimmunogenic and anti-inflammatory characteristics 25,26 Recent efforts use allogeneic BMC, with cells retrieved from healthy donors, cultured, and kept in stock.…”

“…9 Others suggest that transplanted cells fuse with existing cardiomyocytes. 34 Low engraftment and survival of transplanted cells, 16 in addition to limited differentiation, imply that observed improvements in outcomes cannot solely be due to regeneration. 35 Further, some effects are noted within one day, argued as a timeframe too brief for genuine regeneration.…”