Placenta for cardiac tissue engineering

Abstract

Myocardial infarction results in loss of contracting cardiomyocytes, scar tissue formation and subsequently impairment of cardiac performance. Despite the latest advances in the pharmacological and surgical intervention, progressive deterioration of cardiac function due to ventricular remodeling is still observed in a significant proportion of patients. Cardiac tissue engineering developed in recent decades as a new therapeutic approach in growing cardiac tissue grafts for transplantation and replace and repair the injured or diseased myocardium. The major challenge of cardiac tissue engineering is vascularization of engineered tissue grafts for survival of grafts and tissue engraftment and integration with host organs.

In this thesis, we hypothesize using placenta with highly vascularized structure for cardiac tissue engineering. The research is divided in three parts. In the first part of the study, acellular extracellular matrices of porcine amniotic membranes were generated by decellularization and used as scaffold material to fabricate cardiac tissue constructs with neonatal rat cardiomyocytes. The cardiac construct could able to contract synchronously without electrical stimulation. The engineered cardiac patch can integrate with the host myocardium after transplantation in rat myocardial infarction model. The acellular amniotic membrane also supports the growth of human embryonic stem cells and human mesenchymal stem cells in vitro. Integration and neovascularization were observed in Hematoxylin and Eosin staining after transplantation of stem cells seeded matrices in normal rat myocardium. Further studies are awaited to optimize the electrophysiological functioning of the engineered cardiac patch.

The second part of the research is to investigate the functional effect of placenta disc in the cardiac performance after myocardial infarction in rat model. The cardiac function was improved after 4 weeks of transplantation of whole intact placenta disc in rat acute myocardial infarction model by echocardiographic and haemodynamic studies, which achieve a faster cardiac function improvement as compared with intact amniotic membrane transplantation. Cell engraftment was observed after 8 weeks of transplantation in rat ischaemic myocardium without the use of immunosuppressant. The mechanism of action of the placenta disc on improvement of cardiac function remained to be elucidated.

The third part of the research is to develop an injectable form of acellular placenta extracellular matrix as a biomaterial for heart regeneration. Acellular extracellular matrices of rat placenta tissue were generated by perfusion decellularization and solubilized by pepsin to generate the injectable placenta matrices. Intramyocardial injection of the placenta matrices is able to improve the cardiac function after 8 weeks of transplantation in rat acute myocardial infarction model.

Our study in rat model proposed that placenta tissue presents a rich source of biomaterial and stem cells for preserving the cardiac function after acute myocardial infarction. This provides a treatment option for heart failure, and further investigation on the mechanisms of action of the placenta tissues on heart regeneration is warranted before translating into clinical application.