Regenerative medicine aims to achieve functional and structural restoration of a failing organ. Applied to cardiovascular medicine and surgery, this emerging discipline offers a disruptive innovation poised to transform healthcare paradigms by providing the prospect of curative solutions beyond the reach of current standard-of-care. This chapter highlights recent advances fueling this promising multidisciplinary field in the context of heart failure management. Building on breakthroughs in stem cell science, the rapidly evolving regenerative armamentarium leverages natural mechanisms of heart development and lifelong innate rejuvenation. Stem cell therapies seek to boost an otherwise limited aptitude of the human adult myocardium for self-renewal by securing a tissue-specific reparative environment within the failing organ. Supported by favorable preclinical experience, translation of regenerative paradigms has been tested in the clinical setting in both acute and chronic conditions. Meta-analyses of stem cell-based clinical trials underscore the feasibility and safety of regenerative procedures in ischemic heart disease, yet commonly point to modest and variable outcome in parameters of recovery. These initial proof-of-concept trials rely on the use of purified human cells, typically delivered in their native state. Several areas of focus have developed to better establish the scope of clinical use and maximize regenerative benefit. Specifically, next generation trials aim to use the most appropriate cell sources and cell types, enhance cardiogenicity and therapeutic effectiveness, select patient populations most amenable to cell-based therapy, establish ideal timing of intervention, and optimize routes of administration. To inform early adoption in practice, the rigor of comparative effectiveness outcome analysis will ultimately be needed to empower the future of heart failure care, enriched by regenerative strategies that address the unmet needs of a growing patient population.
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