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.

Multilayered fibroblasts constructed by accelerated cellular self-assembly and applications for regenerative medicine

“…Moreover, seeding of single cells requires time for the cells to attach to the area, resulting in loss of some cells before they can attach. This is similar to in vivo situations, where cell therapy by injection of cells fails to deliver the cells to target sites unless biomaterials are used for cell transport (Suzuki et al, 2018). We demonstrate that the 3D-DF can be grafted onto the wounded dermis in vitro.…”