Cardiopoietic Stem Cells for Heart Failure Therapy

Heart failure underlies a growing epidemic of patient populations whose poor outcomes expose the shortcomings of current standards of care. In the context of progressive organ deterioration, left ventricular assist devices and cardiac transplantation remain applicable only in a select number of qualifying patients. Consequently, recurrent hospitalizations and costly life-extending measures have imposed an increased burden on healthcare systems. Patient unmet needs have in turn fueled an emergent focus on the development of "cardioregenerative therapies," aimed at achieving structural and functional tissue restitution. A case in point is the deployment of stem cell-based therapies that leverage recent breakthroughs in developmental biology and use established methods for cell delivery. While in principle feasible and safe, such interventions have largely yielded inhomogeneous benefit in clinical trials. Absence in homogeneity in cellular processing and handling along with divergence in cell phenotypes has been associated with a dichotomy in patient response. Molecular analyses in fact demonstrate that adult-derived cells rarely harbor an innate regenerative potency, in particular in the elderly. Thus, beyond patient stratification, zooming on most adequate timing as well as mode of cell administration, increased emphasis has been placed on decoding intimate stem cell features that predict best clinical outcomes. Accordingly, the latest iteration of cell therapies incorporates targeted optimization strategies, exemplified by cardiopoietic preconditioning, to ensure generalizable benefit in heart failure cohorts and averse or delay the need for cardiac replacement therapy.