Cardiospheres and tissue engineering for myocardial regeneration: potential for clinical application

Abstract

Tissue engineering is an increasingly expanding area of research in the cardiovascular field that involves engineering, chemistry, biology and medicine. Cardiac tissue engineering (CTE) aims to regenerate myocardial damage by combining cells, matrix, biological active molecules and physiological stimuli. The rationale behind CTE applications is that in order to regenerate the ventricular wall after a myocardial infarction it is necessary to combine procedures that regenerate both cardiomyocytes and the extracellular matrix. The application of (stem) cells together with a matrix could represent an environment protected from the inflammatory and pro-apoptotic signals, a stemness/survival reservoir slowly releasing cells and factors promoting tissue regeneration and angiogenesis. This review will focus on the applications and advantages that CTE application could offer compared to conventional cell therapy.

A Novel Closed-Chest Porcine Model of Chronic Ischemic Heart Failure Suitable for Experimental Research in Cardiovascular Disease

“…All research approaches focusing on the improvement of cardiac function by cell therapy have hitherto encountered only incomplete success and generated conflicting results with no clear evidence of heart regeneration potential, which is mainly due to unsolved issues related to low survival and engraftment rate of injected cells, as well as the occurrence of complications such as inflammation or fibrosis [4, 18–20]. In that sense, the scientific community has now to take a step back as the clinical outcome highlighted by the most recent clinical trials has only partially mirrored the expected results based on preclinical animal models, in terms of actual engraftment, survival, differentiation, and functional recovery.…”

Cardiac Cell Therapy: The Next (Re)Generation

“…Therefore an appealing approach to reduce cellular loss and favor engraftment is the application of cells within a matrix, which should provide mechanical support to the damaged ventricle and assure a protected environment for the cells. The ideal matrix should be biodegradable, non-immunogenic, it should support the electro-mechanical properties of the heart and be gradually replaced with newly synthesized ECM [102]. Furthermore, different bioactive molecules can be combined to a specific matrix to grant a controlled release.…”

Secreted proteins as a fundamental source for biomarker discovery

“…Simultaneously, with efforts to identify CPC secretomes and possible paracrine/autocrine factors, numerous studies have been published in few recent years based on engineering of biomaterial scaffolds and sheets, with aim to improve stem cell survival rates and their functions after transplantation into damaged myocardium [43–44]. Since CPCs as well as other progenitor cells are located in tissue in spacial microenvironments (niches) which maintain and regulate them together [45] with present soluble and cell secreted factors, one can imagine, that after injury when surrounding ECM components are lost, the biomaterial can serve as ECM replacement with chemical and biophysical interactions [46–48] and could promote cell survival, function, retention and engraftment. In addition to contribution of CPCs to the repair of heart injury, differentiated cardiomyocytes have been induced to proliferate and regenerate as well [49].…”