Evaluation of Multiple Biological Therapies for Ischemic Cardiac Disease

Abstract

The development of cell-and gene-based strategies for regenerative medicine offers a therapeutic option for the repair and potential regeneration of damaged cardiac tissue post-myocardial infarction (MI). Human umbilical cord subepithelial cell-derived stem cells (hUC-SECs), human bone marrow-derived mesenchymal stem cells (hBM-MSCs), and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), all derived from human tissue, have been shown to have in vitro and in vivo therapeutic potential. Additionally, S100a1, VEGF165, and stromal-derived factor-1a (SDF-1a) genes all have the potential to improve cardiac function and/or effect adverse remodeling. In this study, we compared the therapeutic potential of hBM-MSCs, hUCSECs, and hiPSC-CMs along with plasmid-based genes to evaluate the in vivo potential of intramyocardially injected biologics to enhance cardiac function in a mouse MI model. Human cells derived from various tissue types were expanded under hypoxic conditions and injected intramyocardially into mice that had undergone left anterior descending (LAD) artery ligation. Similarly, plasmids were also injected into three groups of mice after LAD ligation. Seven experimental groups were studied in total: (1) control (saline), (2) hBM-MSCs, (3) hiPSC-CMs, (4) hUC-SECs, (5) S100a1 plasmid, (6) VEGF165 plasmid, and (7) SDF-1a plasmid. We evaluated echocardiography, hemodynamic catheterization measurements, and histology at 4 and 12 weeks postbiologic injection. Significant improvement was observed in cardiac function and contractility in hiPSC-CM and S100a1 groups and a significant reduction in left ventricle scar within the hUC-SEC group and a slight improvement in the SDF-1a and VEGF165 groups compared to the control group. These results demonstrate the potential for new biologic therapies to reduce scar burden and improve contractile function.

Human mesenchymal stem cell sheets in xeno-free media for possible allogenic applications

“…Paracrine MSC properties are important in response to injury in tissue regeneration 71–74 . The hUC-MSC is an attractive candidate for regenerative therapy because of its remarkable paracrine action 22,26 . HGF is involved in the mechanism that induces angiogenesis and inhibits fibrosis, and important to tissue repair 54–58 .…”

“…Human umbilical cord-derived MSCs (hUC-MSCs) used in this study represent a promising allogeneic cell source for stem cell therapy among diverse MSC types, with increasing clinical evidence 22–25 . hUC-MSCs exhibit low HLA expression and higher paracrine effects compared to human bone marrow stem cells (hBM-MSC) 22,26,27 . Furthermore, intravenously infused allogenic hUC-MSC treatments induced no adverse host immune responses and produced clinically significant improvements in patients either with heart failure, with spinal cord, or with multiple sclerosis 22–25 .…”

Amelioration of Endoplasmic Reticulum Stress by Mesenchymal Stem Cells via Hepatocyte Growth Factor/c-Met Signaling in Obesity-Associated Kidney Injury

“…Moreover, in addition to the preserved differentiation and immunomodulation capacity compared with BM-MSCs, iPS-MSCs have been demonstrated to be superior with higher accessibility, less oncogenicity, and greater expandability to overcome the inherent limitations in BM-MSCs for clinical application [11][12][13]. Preclinical studies have shown great success in applying iPS-MSCs for treating renal ischemia/reperfusion injury [14], ischemic cardiac disease [15], chronic obstructive pulmonary disease [16], and osteoarthritis [17]. We recently showed that iPS-MSCs conferred renoprotection in adriamycin nephrosis [18], supporting the potential of iPS-MSCs in treating kidney diseases.…”

Isolation of endothelial progenitor cells from human adipose tissue

“…(Imai et al, 2016;Kang et al, 2016;Lukasiewicz, 2016;von Segesser et al, 2016). Stem cell transplantation is a candidate therapy that has recently been tested to treat ischemia-related diseases, such as stroke (Kasahara et al, 2016;Vahidy et al, 2016;Wang et al, 2016), heart infarction (Henry et al, 2016;Li et al, 2016;Winters et al, 2016), and hindlimb ischemia (Kishimoto et al, 2016;Shin et al, 2016;Yoshida et al, 2016). There are two kinds of stem cells mainly used in transplantation studies; these include mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs).…”