Insight into merits and limitations of direct reprogramming strategies for cardiac regeneration

Direct reprogramming or Transdifferentiation is a way of inducing changes in the cell type from one lineage into another lineage, bypassing pluripotency. This approach is an innovative choice to replace the lost cardiomyocytes after an end-stage myocardial infraction because transplantation is the only feasible remedial option at present. According to the World Health Organization (WHO) estimates, a staggering 17.9 million casualties are reported worldwide each year due to myocardial infarction. It is also the leading cause of death, with an estimated 31% of all deaths globally, which clearly outlines the inadequacies in the current cardiac therapy.

Today, only a handful of cell therapy-based strategies that include induced pluripotent stem cells, embryonic stem cells, bone marrow, liposuction, heart biopsies are known to restore the function of cardiomyocytes after myocardial infarction. Yet, the risks associated with the cell therapy-based strategies necessitate an alternative strategy that satisfies all standards necessary for safe and efficacious reprogramming. To overcome the perils of iPSC cell-based therapies, transdifferentiation of cardiac fibroblasts using microRNAs (miRNAs, miRs) hold a promising role in repair and regeneration. Extensive research in this regard has made it possible to identify an ideal reprogramming cocktail for high yield of reprogrammed cells. However, there is no ideal strategy available with an optimal delivery method for genetic reprogramming.

Researchers from Bio-Nano Electronics Research Centre (BNERC), Toyo University, Japan, present a review that provides an overview and understanding of the direct reprogramming strategies focusing on the merits and the limitations of the strategies. The review also discusses various miRNA delivery strategies for safe, effective, and sustained delivery to achieve better tissue repair with a primary focus on biomaterials like electrospun scaffolds and nanoparticles as potential non-viral vectors. The reviewers emphasize that customized biomaterial-based scaffolds with miRNA not only co-exist with the tissue by providing an intramyocardial cellular environment but also provides precision control of miRNA release that may be crucial for direct cardiac reprogramming. The review has been published in Current Pharmaceutical Design.