Cardiac regenerative medicine represents a promising strategy aimed at restoring impaired heart function by replacing or repairing damaged myocardial tissues, particularly following myocardial infarction (MI), and in heart failure (HF). Although stem cell (SC)-based therapies have demonstrated considerable potential in preclinical studies, their translation into consistent clinical benefits remains challenging. A major obstacle impeding broader success involves extensive SC death occurring post-transplantation due to the adverse hypoxic environment of the diseased myocardium. Recent literature highlights that the beneficial effects of SC therapies rely predominantly on paracrine signaling-mediated tissue repair mechanisms, while their limited therapeutic efficiency correlates with post-implantation cell loss. Despite advances, current regenerative approaches have not effectively addressed critical barriers including insufficient cell viability, suboptimal cell homing, and ineffective integration and retention postdelivery, emphasizing a need for innovative translational solutions.

This Research Topic aims to bridge the translational gap in cardiac SC-based therapies, emphasizing strategies that enhance SC viability, homing, and integration within ischemic/infarcted/failing myocardial tissues. The central objectives include elucidating state-of-the-art knowledge regarding cardiac remodeling post-MI and progression to HF, defining cellular and molecular pathways relevant to SC survival and function, and proposing novel translational delivery systems or surgical methods that can significantly increase therapeutic efficacy and viability outcomes. Emphasis will be given to clinical approaches that address hypoxia-induced SC death and optimized SC integration and functionality in both acute and chronic cardiac pathologies.

To gather further insights within the boundaries of translating SC therapies into clinically viable solutions, we welcome articles addressing, but not limited to, the following themes:

o Advances in material biocompatibility, surface functionalization (nanocoatings, bioactive peptides, growth factors), and improvement in mechanical properties to enhance SC engraftment and viability;

o Elucidation and modulation of signaling pathways (e.g., Wnt/β-catenin, MAPK, PI3K/Akt, FAK) in conjunction with miRNA (e.g., miR21, miR204) and exosomal approaches, and disrupted innate tissue ionic gradients (e.g., acidosis) to facilitate SC adaptation, survival, and remodeling in ischemic/infarcted/failing myocardial environments;

o Immunomodulatory strategies targeting regulating/inflammatory/anti-inflammatory signaling responses post-implantation (e.g., M0, M1, and M2 macrophage phenotypes, pathways activated/suppressed to disrupt extracellular matrix deposition (e.g., via the mediation of (among others) TGF-β, matrix metalloproteinases, interleukins (IL-1, IL-6), and NF-κB)) to improve cell retention and bioactivity;

o Neovascularization, metabolic, and electromechanical effects attributed to enhanced integration of implanted SCs, and prevention of tumorigenicity risk profiles;

o Novel bioengineering approaches including direct, passive (scaffolds, gels), active (pumps, bioreactors), and integrated delivery platforms enhancing SC survival and function;

o Clinical imaging strategies for real-time tracking of cells and for monitoring viability, migration, and integration after transplantation;

o Improved surgical techniques, optimization of implantation/biomolecular injection timing, technical refinements in surgical delivery, practical surgical implications, regulatory issues/requirements, and formulation of effective postoperative care and noninvasive monitoring protocols.

Authors are encouraged to submit manuscripts including original research articles, comprehensive reviews, method papers, and perspectives relevant to the translational advancement of cardiac SC therapies.

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Enhancing Cardiac Regeneration Through Innovative Translational Strategies to Optimize Stem Cell Survival After Implantation