Heart muscle engineering: An update on cardiac muscle replacement therapy

Abstract

Cardiac muscle engineering aims at providing functional myocardium to repair diseased hearts and model cardiac development, physiology, and disease in vitro. Several enabling technologies have been established over the past 10 years to create functional myocardium. Although none of the presently employed technologies yields a perfect match of natural heart muscle, it can be anticipated that human heart muscle equivalents will become available after fine tuning of currently established tissue engineering concepts. This review provides an update on the state of cardiac muscle engineering and its utilization in cardiac regeneration. We discuss the application of stem cells including the allocation of autologous cell material, transgenic technologies that may improve tissue structure as well as in vivo engraftment, and vascularization concepts. We also touch on legal and economic aspects that have to be considered before engineered myocardium may eventually be applied in patients and discuss who may be a potential recipient.

Engineered Early Embryonic Cardiac Tissue Increases Cardiomyocyte Proliferation by Cyclic Mechanical Stretch via p38-MAP Kinase Phosphorylation

“…Several approaches to increase the number of CMs within injured myocardium have been attempted, including (1) activation and stimulation of host myocardial regeneration by transplanted cells via angiogenic and=or paracrine effects, 4,5 (2) direct transplantation of functional CMs or myogenic cells, [6][7][8] and (3) implantation of tissue constructs containing CMs. 9,10 In the latter two cases, the ideal donor CMs possess a high potential for division during cell preparation and potential for further proliferation following implantation to form a viable myocardial tissue within the surrounding injured recipient myocardium. Stem cell-derived CMs are considered as an alternative cell source for cardiac repair.…”

“…11,12 Studies suggest that fetal, finitely proliferating CMs display the best cell survival, functional integration, and sustained cardiac recovery and that three-dimensional (3D) in vitro culture conditions may be optimal for donor CM preparation. 9,[13][14][15] Tissue-engineered cardiac tissue constructs provide the necessary 3D environment for efficient cell survival, functional integration, and sustained cardiac recovery. 9,10 We have recently developed a 3D engineered early embryonic cardiac tissue (EEECT) with similar cell proliferative activity and contractile properties to native developing 1 Cardiovascular Development Research Program, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.…”

“…9,[13][14][15] Tissue-engineered cardiac tissue constructs provide the necessary 3D environment for efficient cell survival, functional integration, and sustained cardiac recovery. 9,10 We have recently developed a 3D engineered early embryonic cardiac tissue (EEECT) with similar cell proliferative activity and contractile properties to native developing 1 Cardiovascular Development Research Program, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania. Departments of 2 Bioengineering and 3 Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania.…”

Intravital microscopy to study myocardial engraftment

“…In vitro engineered neonatal myocardial sheets of thicknesses up to 200 μm survive, become vascularized and electrically coupled with the host myocardial cells when grafted onto the surface of an infarcted heart [10]. Myocardial tissue could be engineered in larger amount and thickness in vivo using femoral arteriovenous loop enclosed in a subcutaneous chamber [11].…”

Rapid Prototyping of Engineered Heart Tissues through Miniaturization and Phenotype-Automation

“…Each year, nearly seven thousand patients in the United States die while waiting for an organ transplant [1]. Developing heart muscles in vitro for transplantation [3] [4] is one approach that could ultimately overcome this critical shortage. For complex tissues such as a heart muscle, the final product has to mimic physiological functions as well as the regulatory system for regenerating the recipient's tissue functions.…”