This review aims to highlight the normal physiological remodeling that occurs in healthy aging hearts, including changes that occur in contractility, conduction, valve function, large and small coronary vessels, and the extracellular matrix. These “normal” age-related changes serve as the foundation that supports decreased plasticity and limited ability for tissue remodeling during pathophysiological states such as myocardial ischemia and heart failure. This review will identify populations at greater risk for poor tissue remodeling in advanced age along with present and future therapeutic strategies that may ameliorate dysfunctional tissue remodeling in aging hearts.

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Pathologies of the vasculature and microvasculature are often complex in nature, leading to loss of physiological homeostatic regulation of patency and adequate perfusion to match tissue metabolic demands. Contributing pathological factors include endothelial dysfunction, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, loss of angiogenic potential and vascular density, and greater senescence and apoptosis. In many clinical settings, current pharmacologic strategies lack holistic mechanisms whilst addressing symptoms of pathology rather than their root cause. To address this, efforts have been heavily focused on cellular therapies that can tackle the multifaceted etiology of vascular and microvascular dysfunction. In this review, we discuss 1) the state of the field in terms of common therapeutic cell population isolation techniques, their unique characteristics and their advantages and disadvantages, 2) common molecular mechanisms of cell therapies to restore vascularization and/or vascular function, 3) arguments for and against allogenic vs. autologous applications of cell therapies, 4) emerging strategies to optimize and enhance cell therapies through priming and preconditioning, and finally, 5) emerging dosing and administrative strategies to bolster therapeutic effect. Significant clinical and animal studies of emerging cellular therapies to restore vascular function or pathologic tissue health by way of improved vascularization are highlighted throughout these sections.