Impact of Biomaterials on Differentiation and Reprogramming Approaches for the Generation of Functional Cardiomyocytes

Abstract

The irreversible loss of functional cardiomyocytes (CMs) after myocardial infarction (MI) represents one major barrier to heart regeneration and functional recovery. The combination of different cell sources and different biomaterials have been investigated to generate CMs by differentiation or reprogramming approaches although at low efficiency. This critical review article discusses the role of biomaterial platforms integrating biochemical instructive cues as a tool for the effective generation of functional CMs. The report firstly introduces MI and the main cardiac regenerative medicine strategies under investigation. Then, it describes the main stem cell populations and indirect and direct reprogramming approaches for cardiac regenerative medicine. A third section discusses the main techniques for the characterization of stem cell differentiation and fibroblast reprogramming into CMs. Another section describes the main biomaterials investigated for stem cell differentiation and fibroblast reprogramming into CMs. Finally, a critical analysis of the scientific literature is presented for an efficient generation of functional CMs. The authors underline the need for biomimetic, reproducible and scalable biomaterial platforms and their integration with external physical stimuli in controlled culture microenvironments for the generation of functional CMs.

MicroRNA-Mediated Direct Reprogramming of Human Adult Fibroblasts Toward Cardiac Phenotype

“…AHCFs transfected with miRcombo were able to maintain the expression of specific cardiomyocyte markers at the tested time points (7 and 15 days). Future studies will be addressed to thoroughly study miRcombomediated direct reprogramming of AHCFs at longer times and under different microenvironmental stimulations, and to develop non-viral vectors for in situ transfection with miRcombo, paving the way toward a clinical translation of direct reprogramming strategies (Muraoka et al, 2014;Li et al, 2016;Paoletti et al, 2018).…”

Bioengineering Methods in MicroRNA-Mediated Direct Reprogramming of Fibroblasts Into Cardiomyocytes

“…Given the poor endogenous regenerative potential of the adult heart, recovery of cardiac functionality could be accomplished by the replenishment of lost CMs. However, cell therapies and cardiac tissue engineering strategies have achieved limited success due to poor engrafting, survival, and integration of implanted cells, alone or in combination with biomaterials, into the host tissue and the unmet need for a source of mature and functional CMs (1)(2)(3)(4).…”

“…Ischemic heart disease is a major cause of mortality with more than 23 million cases worldwide ( 1 , 2 ). During myocardial infarction (MI), billions of cardiomyocytes (CMs) are irreversibly lost and replaced by cardiac fibroblasts (CFs) forming a non-contractile scar tissue, which undergoes continuous remodeling, causing left ventricle dilation and progressive heart failure ( 3 , 4 ). Given the poor endogenous regenerative potential of the adult heart, recovery of cardiac functionality could be accomplished by the replenishment of lost CMs.…”

Tissue engineering strategies for the induction of angiogenesis using biomaterials

“…ESCs could be isolated from blastocysts inner cell mass having the ability to give rise to any cell type and to produce endodermal-, mesodermal-, and ectodermal-derived lineages and SCs [33]. Recent researches indicated an inherent ability of ESCs in differentiating into EC-, α-SMC- and cardiomyocyte-like cells as well [34]. During endothelial differentiation of ESCs, cell distribution of specific markers such as CD31 (PECAM), von Willebrand factor is increased.…”