Induced regeneration—the progress and promise of direct reprogramming for heart repair

Abstract

Regeneration of cardiac tissue has the potential to transform cardiovascular medicine. Recent advances in stem cell biology and direct reprogramming, or transdifferentiation, have produced powerful new tools to advance this goal. In this Review we examine key developments in the generation of new cardiomyocytes in vitro as well as the exciting progress that has been made toward in vivo reprogramming of cardiac tissue. We also address controversies and hurdles that challenge the field.

Direct Reprogramming of Fibroblasts into Cardiomyocytes for Cardiac Regenerative Medicine

“…Some studies evaluated the activation of cardiac-specific genes in reprogrammed iCMs by Q-PCR and/or histological immunostaining, which has lower stringency than methods such as global transcriptome analysis, CM-specific epigenetic marks, Ca 2+ handling, electrophysiological properties, and cellular contraction. 23 Nevertheless, the summary of findings (listed in Table 1) suggests that endogenous cardiac fibroblasts could become a viable cell source to generate new iCMs as a replacement of damaged CMs in the heart. Indeed, investigations aiming to identify the most ideal combination of reprogramming factors are also developing new approaches to study and validate the molecular networks that can establish cardiac cell fate.…”

“…[16][17][18] Several reviews highlight the potential and challenges of this new avenue for cardiac regenerative medicine. [19][20][21][22][23][24] In this review, we consider the approaches and characterization of in vitro ( Table 1) and in vivo ( Table 2) reprogrammed iCMs reported from different laboratories. We hope that this up-to-date discussion will help outline the major challenges of this new approach, and summarize future efforts needed to translate it toward a practical therapy for damaged hearts.…”

Heart Regeneration

“…Many different strategies aiming to revert, palliate, or ameliorate the deleterious effects of heart failure have been intensively pursued, and excellent reviews on the topic exist. [1][2][3] Briefly, approaches used to tackle cardiac repair have been focused mainly on the use of stem cells to replenish lost muscle mass (cell transplantation or mobilization of resident cardiac stem cells), reduction of cardiomyocyte hypertrophy or prevention of fibrosis, promotion of angiogenesis, and, most recently, in vivo reprogramming strategies. [4][5][6] Although these significant advances are contributing to the development of more efficient therapies, successful and efficient heart repair strategies are by and large still lacking.…”

Reprogramming Approaches to Cardiovascular Disease: From Developmental Biology to Regenerative Medicine

“…We and others have also directly converted human cardiac and dermal fibroblasts into cardiac cells [11][12][13]. Several review papers published from different labs illustrate the potential and challenges of this new avenue for cardiac regenerative medicine [14][15][16][17][18][19].…”