Differentiation of Adipose Tissue-Derived Stem Cells into Cardiomyocytes: An Overview

Cardiovascular diseases, including congenital and acquired cardiovascular diseases, impose a severe burden on healthcare systems worldwide. Although bone marrow-derived stem cells (BMSCs) therapy can be an effective therapeutic strategy for the heart disease, relatively low abundance, difficult accessibility, and small tissue volume hinder the clinical usefulness. Adipose tissue-derived stem cells (ADSCs) show similar potential with BMSCs to differentiate into lineages and tissues, such as smooth muscle cells, endothelial cells, and adipocytes, with attractiveness of obtaining adipose tissue easily and repeatedly, and a simple separation procedure. We briefly summarize the current understanding of the cardiomyocytes differentiated from ADSCs

An ApoA-I Mimic Peptide of 4F Promotes SDF-1α Expression in Endothelial Cells Through PI3K/Akt/ERK/HIF-1α Signaling Pathway

Atherosclerosis (AS) seriously impairs the health of human beings and is manifested initially as endothelial cells (ECs) impairment and dysfunction in vascular intima, which can be alleviated through mobilization of endothelial progenitor cells (EPCs) induced by stromal-cell-derived factor-1α (SDF-1α). A strong inverse correlation between HDL and AS has been proposed. The aim of the present work is to investigate whether 4F, an apolipoprotein A-I (apoA-I, major component protein of HDL) mimic peptide, can upregulate SDF-1α in mice and human umbilical vein endothelial cells (HUVECs) and the underlying mechanism. The protein levels of SDF-1α were measured by ELISA assay. Protein levels of HIF-1α, phosphorylated Akt (p-Akt), and phosphorylated ERK (p-ERK) were evaluated by Western blotting analysis. The results show that L-4F significantly upregulates protein levels of HIF-1α, Akt, and ERK, which can be inhibited by the PI3K inhibitor, LY294002, or ERK inhibitor, PD98059, respectively. Particularly, LY294002 can downregulate the levels of p-ERK, while PD98059 cannot suppress that of p-Akt. D-4F can upregulate the levels of HIF, p-Akt, and p-ERK in the abdominal aorta and inferior vena cava from mice. These results suggest that 4F promotes SDF-1α expression in ECs through PI3K/Akt/ERK/HIF-1α signaling pathway.

The Contribution of Liver Sinusoidal Endothelial Cells to Clearance of Therapeutic Antibody

Many chronic inflammatory diseases are treated by administration of “biological” therapies in terms of fully human and humanized monoclonal antibodies or Fc fusion proteins. These tools have widespread efficacy and are favored because they generally exhibit high specificity for target with a low toxicity. However, the design of clinically applicable humanized antibodies is complicated by the need to circumvent normal antibody clearance mechanisms to maintain therapeutic dosing, whilst avoiding development of off target antibody dependent cellular toxicity. Classically, professional phagocytic immune cells are responsible for scavenging and clearance of antibody via interactions with the Fc portion. Immune cells such as macrophages, monocytes, and neutrophils express Fc receptor subsets, such as the FcγR that can then clear immune complexes. Another, the neonatal Fc receptor (FcRn) is key to clearance of IgG in vivo and serum half-life of antibody is explicitly linked to function of this receptor. The liver is a site of significant expression of FcRn and indeed several hepatic cell populations including Kupffer cells and liver sinusoidal endothelial cells (LSEC), play key roles in antibody clearance. This combined with the fact that the liver is a highly perfused organ with a relatively permissive microcirculation means that hepatic binding of antibody has a significant effect on pharmacokinetics of clearance. Liver disease can alter systemic distribution or pharmacokinetics of antibody-based therapies and impact on clinical effectiveness, however, few studies document the changes in key membrane receptors involved in antibody clearance across the spectrum of liver disease. Similarly, the individual contribution of LSEC scavenger receptors to antibody clearance in a healthy or chronically diseased organ is not well characterized. This is an important omission since pharmacokinetic studies of antibody distribution are often based on studies in healthy individuals and thus may not reflect the picture in an aging or chronically diseased population. Therefore, in this review we consider the expression and function of key antibody-binding receptors on LSEC, and the features of therapeutic antibodies which may accentuate clearance by the liver. We then discuss the implications of this for the design and utility of monoclonal antibody-based therapies.