Regenerative principles enrich cardiac rehabilitation practice

Abstract

Cardiovascular morbidity imposes a high degree of disability and mortality, with limited therapeutic options available in end-stage disease. Integral to standard of care, cardiac rehabilitation aims on improving quality-of-life and prolonging survival. The recent advent of regenerative technologies paves the way for a transformative era in rehabilitation medicine whereby, beyond controlling risk factors and disease progression, the prospect of curative solutions is increasingly tangible. To date, the spectrum of clinical experience in cardiac regenerative medicine relies on stem cell-based therapies delivered to the diseased myocardium either acutely/subacutely, after a coronary event, or in the setting of chronic heart failure. Application of autologous/allogeneic stem cell platforms has established safety and feasibility, with encouraging signals of efficacy. Newer protocols aim to purify cell populations in an attempt to eliminate nonregenerative and enrich for regenerative cell types before use. Most advanced technologies have been developed to isolate resident cell populations directly from the heart or, alternatively, condition cells from noncardiac sources to attain a disease-targeted lineage-specified phenotype for optimized outcome. Because a multiplicity of cell-based technologies has undergone phase I/II evaluation, pivotal trials are currently underway in larger patient populations. Translation of regenerative principles into clinical practice will increasingly involve rehabilitation providers across the continuum of patient care. Regenerative rehabilitation is thus an emerging multidisciplinary field, full of opportunities and ready to be explored.

Figure 1. Differences in harvest, processing and delivery of First Generation, Purified and Next Generation progenitors

First Generation stem cells are harvested from source tissue and delivered without significant processing as mixed progenitor pools. In contrast, Purified biologics utilize a cell purification step to isolate specific cell phenotypes from source tissue, eliminating cells devoid of regenerative benefit. Next Generation stem cell therapy introduces the concept of lineage specification by either harvesting regenerative stem cells from the heart, or by guiding them with a process termed cardiopoiesis to yield a pure population of progenitors guided for maximal regenerative potency.