Abstract
Despite significant progress in treating ischemic cardiac disease and succeeding heart failure, there is still an unmet need to develop effective therapeutic strategies given the persistent high-mortality rate. Advances in stem cell biology hold great promise for regenerative medicine, particularly for cardiac regeneration. Various cell types have been used both in preclinical and clinical studies to repair the injured heart, either directly or indirectly. Transplanted cells may act in an autocrine and/or paracrine manner to improve the myocyte survival and migration of remote and/or resident stem cells to the site of injury. Still, the molecular mechanisms regulating cardiac protection and repair are poorly understood. Stem cell fate is directed by multifaceted interactions between genetic, epigenetic, transcriptional, and post-transcriptional mechanisms. Decoding stem cells’ “panomic” data would provide a comprehensive picture of the underlying mechanisms, resulting in patient-tailored therapy. This review offers a critical analysis of omics data in relation to stem cell survival and differentiation. Additionally, the emerging role of stem cell-derived exosomes as “cell-free” therapy is debated. Last but not least, we discuss the challenges to retrieve and analyze the huge amount of publicly available omics data.
Highlights
Morbidity and mortality caused by ischemic heart disease (IHD) and subsequent heart failure (HF) are still high, despite modern treatments
The study conducted by Medina and colleagues provides a broad molecular fingerprint of two endothelial progenitor cell (EPC) subtypes categorized according to the time at which they appear in culture: early EPCs and outgrowth endothelial cells (OECs), emphasizing once again the differences between them. These cells have strikingly different gene expression signatures: early EPCs proved to be enriched in haematopoietic-specific transcripts, while OECs highly expressed transcripts involved in vascular development and angiogenesis [54]
These data are of particular importance when in pursuit of possible candidates for prompting therapeutic angiogenesis; OECs could be a suitable choice for cardiac protection and regeneration, as opposed to early EPCs
Summary
Morbidity and mortality caused by ischemic heart disease (IHD) and subsequent heart failure (HF) are still high, despite modern treatments. In-depth exploration mechanisms of SC-mediated protection and cardiac regeneration is critically needed in order to achieve efficient and safe SCT. Stem cell (SC) fateand can limitations be regulated by various identified for each category of omic data. Metabolites) provided to improve cardiac regeneration and achieve patient-tailored. Provided useful tools to improve cardiac regeneration and achieve patient-tailored therapy. The use of DNMT inhibitors is limited by alterations that affect their differentiation potential and tumorigenicity. Agents/targets are hindered by off-target effect due to their ability to regulate genetic networks and Priming SCs with pro-survival or angiogenic factors and genetic engineering of SCs to overexpress not a single pathway. Priming SCs with pro-survival or angiogenic factors and genetic engineering of beneficial signals require synergistic action for a significant effect.
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