A brief review: adipose-derived stem cells and their therapeutic potential in cardiovascular diseases

Abstract

Adipose-derived stem cells (ADSCs) are easily obtained and expanded, and have emerged as a novel source of adult stem cells for the treatment of cardiovascular diseases. These cells have been shown to have the capability of differentiating into cardiomyocytes, vascular smooth muscle cells, and endothelial cells. Furthermore, ADSCs secrete a series of paracrine factors to promote neovascularization, reduce apoptosis, and inhibit fibrosis, which contributes to cardiac regeneration. As a novel therapy in the regenerative field, ADSCs still face various limitations, such as low survival and engraftment. Thus, engineering and pharmacological studies have been conducted to solve these problems. Investigations have moved into phase I and II clinical trials examining the safety and efficacy of ADSCs in the setting of myocardial infarction. In this review, we discuss the differentiation and paracrine functions of ADSCs, the strategies promoting their therapeutic efficacy, and their clinical usage.

Keywords: Adipose-derived stem cells; Cardiovascular diseases; Differentiation; Paracrine effect; Stem cell transplantation.

Fig. 1

Differentiation ability of adipose-derived stem cells. ADSCs can differentiate into cardiovascular lineages, such as cardiomyocytes, endothelial cells, vascular smooth muscle cells, and pacemaker cells. Various reagents have been used for ADSC induction. Ang angiotensin, Aza azacytidine, bFGF basic fibroblast growth factor, IGF insulin-like growth factor, SPC sphingosylphosphorylcholine, TBX-18 T-box 18, TGF transforming growth factor, TXA ₂ thromboxane A₂, VEGF vascular endothelial growth factor

Fig. 2

Paracrine effects of adipose-derived stem cells (ADSCs). ADSCs secrete vascular endothelial growth factor (VEGF), microRNA (miR)-31, miR-126, and exosomes for promoting neovascularization. The anti-apoptosis effect of ADSCs is mediated by insulin-like growth factor-1 (IGF-1) and miR-301a. The anti-cardiac remodeling effect is associated with hepatocyte growth factor (HGF). ADSC-derived exosomes inhibit mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH-kinase (PI3K) pathways, exerting an anti-vascular remodeling effect

Fig. 3

Engineered and pharmacologically modified adipose-derived stem cells (ADSCs). A summary of engineering and pharmacological strategies for improving survival and retention of transplanted ADSCs in ischemic hearts is shown, such as three-dimensional (3D) cultured ADSCs combined with self-assembling peptide (SAP), magnetic nanoparticle-loaded ADSCs, encapsulated ADSCs with chitosan and hydrogel, ADSC patch, and pharmacologically modified ADSCs