Stem cell death and survival in heart regeneration and repair

Abstract

Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function.

Alginate‐gelatin encapsulation of human endothelial cells promoted angiogenesis in in vivo and in vitro milieu

“…It seems that direct injection of HUVECs caused an extensive cell spread into muscular niche and lack of appropriate cell connection, resulting in the failure of microvascular formation. Suitable reorganization of matrix is thought to be essential in dynamics of cells after transplantation (Abdelwahid et al, ). In unfavorable condition, a large fraction of injected cells show apoptotic cell death due to lack of cell‐to‐cell cross‐talk and interaction with ECM (Li, Bennett, & Wang, ).…”

Apoptosis on the move

“…Apoptosis also published a number of high-impact reviews that are worth mentioning. These papers were on the mitochondrial dynamics in maintaining cell integrity and preventing carcinogenesis [8], stem cell death and survival in heart regeneration and repair [9] and macroautophagy and mitochondrial ROS in cancer therapy [10]. …”

Cardiovascular Regenerative Technologies: Update and Future Outlook

“…Although clinical trials based on the intra-myocardial injection of single-cell suspensions have been performed with mesenchymal autologous cells, the interpretation of the results is controversial and roused questions and doubts regarding the power of the technology [8,9,10]. There is currently a consensus regarding the possible reasons for the single-cell suspension therapy failure; the negative results are addressed to the scarce survival and retention of the cells at the level of the infarcted area [11]. The newest regenerative approaches aim at enhancing survival, grafting, and retention abilities of the injected cells using different methodologies.…”