Human Cardiac-Mesenchymal Stem Cell-Like Cells, a Novel Cell Population with Therapeutic Potential.

Rachel Oldershaw,Lissette Magana,Annette Meeson,W Andrew Owens,Martin Linney,Gendie E Lash,Rachel Liddle,Gavin Richardson,Jason H Gill,Rachel Sutherland

doi:10.1089/scd.2018.0170

Abstract

Cardiac stem/progenitors are being used in the clinic to treat patients with a range of cardiac pathologies. However, improvements in heart function following treatment have been reported to be variable, with some showing no response. This discrepancy in response remains unresolved. Mesenchymal stem cells (MSCs) have been highlighted as a regenerative tool as these cells display both immunomodulatory and proregenerative activities. The purpose of this study was to derive a cardiac MSC population to provide an alternative/support to current therapies. We derived human cardiac-mesenchymal stem cell-like cells (CMSCLC), so named as they share some MSC characteristics. However, CMSCLC lack the MSC trilineage differentiation capacity, being capable of only rare adipogenic differentiation and demonstrating low/no osteogenic or chondrogenic potential, a phenotype that may have advantages following transplantation. Furthermore, CMSCLC expressed low levels of p16, high levels of MHCI, and low levels of MHCII. A lack of senescent cells would also be advantageous for cells to be used therapeutically, as would the ability to modulate the immune response. Crucially, CMSCLC display a transcriptional profile that includes genes associated with cardioprotective/cardiobeneficial effects. CMSCLC are also secretory and multipotent, giving rise to cardiomyocytes and endothelial cells. Our findings support CMSCLC as a novel cell population suitable for use for transplantation.

Highlights

Cellular strategies using bone marrow-derived cells or autologous cardiac-derived cells have translated into the clinical setting as potential therapies for the treatment of patients with heart failure [1,2,3]
cardiac-mesenchymal stem cell-like cells (CMSCLC) from three different patient-derived cultures readily formed similar numbers of CFUs around day 15 postseeding into culture (Fig. 1G) as control BM-Mesenchymal stem cells (MSCs) were used and formed CFUs at day 7 postseeding in vitro, CFUs were counted at day 15 (Fig. 1G)
Both cell populations exhibited low adipogenic differentiation and both failed to undergo chondrogenesis. This contrasts with bone marrow-derived MSCs (BM-MSCs) and subendocardial MSCs that have this trilineage differentiation potential [9]. These differences might be due to these being distinct cell populations, differences in tissue used for cell derivation, or due to differences in culture conditions used

Summary

Introduction

Cellular strategies using bone marrow-derived cells or autologous cardiac-derived cells have translated into the clinical setting as potential therapies for the treatment of patients with heart failure [1,2,3] These trials have demonstrated some benefits of these therapies, they are not without limitations, with reports of only modest improvements in cardiac function in some patients and no improvements in others. Human subendocardial MSCs have been derived; this cell population was capable of expansion in vitro, expressed markers normally expressed by MSCs, and was capable of multilineage differentiation to osteoblasts, adipocytes, and chondrocytes. These cells express cardiac transcription factors while lacking expression of markers associated with mature cardiomyocytes [9]

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