Where are Cell-Based Therapies Heading? Current Limitations and Future Directions

Abstract

Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause
of morbidity and mortality worldwide. Its prevalence is increasing despite advances in medical
and device therapies. Adult stem cell therapies have emerged as a promising treatment generating
new cardiomyocytes and vessels, and are anticipated to reverse functional deterioration in
patients with congestive heart failure for whom heart transplantation is the only cure. This field
was enthusiastically studied in last two decades, revealing that the major beneficial outcomes
from cell therapy are associated with paracrine effects rather than direct differentiation. Accordingly,
paracrine factors (e.g., growth factors, cytokines and microRNAs) secreted from
stem cells reduce scar volume and myocyte apoptosis, increase myocyte proliferation and activate
endogenous cardiac stem cells to produce new myocytes. Moreover, functional efficacy
of progenitor cells isolated from the bone marrow, adipose tissue and the heart have shown
promising effects in preclinical animal models. These convincing results led to the initiation of
clinical trials using autologous and allogeneic stem cells, and progenitor cells. Although clinical
trials demonstrated their safety in humans, therapeutic efficacy is still inconclusive. This
review discusses the progress and limitations of cell-based therapies and alternative solutions
for future advancement.
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