Short-term mechanical stretch fails to differentiate human adipose-derived stem cells into cardiovascular cell phenotypes

Abstract

BackgroundWe and others have previously demonstrated that adipose-derived stem cells (ASCs) transplantation improve cardiac dysfunction post-myocardium infarction (MI) under hemodynamic stress in rats. The beneficial effects appear to be associated with pleiotropic factors due to a complex interplay between the transplanted ASCs and the microenvironment in the absence of cell transdifferentiation. In the present work, we tested the hypothesis that mechanical stretch per se could change human ASCs (hASCs) into cardiovascular cell phenotypes that might influence post-MI outcomes.MethodsHuman ASCs were obtained from patients undergoing liposuction procedures. These cells were stretched 12%, 1Hz up to 96 hours by using Flexercell 4000 system. Protein and gene expression were evaluated to identify cardiovascular cell markers. Culture medium was analyzed to determine cell releasing factors, and contraction potential was also evaluated.ResultsMechanical stretch, which is associated with extracellular signal-regulated kinase (ERK) phosphorylation, failed to induce the expression of cardiovascular cell markers in human ASCs, and mesenchymal cell surface markers (CD29; CD90) remained unchanged. hASCs and smooth muscle cells (SMCs) displayed comparable contraction ability. In addition, these cells demonstrated a profound ability to secrete an array of cytokines. These two properties of human ASCs were not influenced by mechanical stretch.ConclusionsAltogether, our findings demonstrate that hASCs secrete an array of cytokines and display contraction ability even in the absence of induction of cardiovascular cell markers or the loss of mesenchymal surface markers when exposed to mechanical stretch. These properties may contribute to beneficial post-MI cardiovascular outcomes and deserve to be further explored under the controlled influence of other microenvironment components associated with myocardial infarction, such as tissue hypoxia.

Enhanced cardiomyogenic induction of mouse pluripotent cells by cyclic mechanical stretch

“…It is notable that while we focus on the stretch induction of functional CM differentiation from precursors, there have been studies on the stretch control of “already-committed” or “matured” CMs [21–23] (see our review [4]). These studies have dealt with physiological stretch conditions which already-differentiated CMs will see in vivo (about 10% strain and 1 Hz frequency, values similar to our study and others described above for differentiation purpose [7,11,12,18]). While these ranges are generally accepted as physiologically relevant, our prescreening result suggests a need for fine tuning to better trigger beating CM development.…”

“…Comparison of stretch regimens to induce functional CM development may not be fully feasible at this stage with limited number of reports using different precursors [7,11,12,18]. In our preliminary screening, stretch amplitudes of 5% and 10% at 1 Hz for 24 h provided less strong beating colony formation and relatively slower beating.…”

“…Exploiting this concept, a few recent studies begun to test the effects of mechanical stretch in inducing cardiomyogenesis, but reported varying outcomes. Adipose MSCs exposed to stretch (12% cyclic strain at 1 Hz for 96 h) failed to express cardiac markers [11]. For bone marrow MSCs treated with stretch (5–20% strain, 1 Hz, 24–72 h), CM markers (GATA4, Nkx 2.5, MEF2c) could be detected but beating cells were not produced [12].…”

“…Results with stretch loading, however, indicated varying outcomes. For example, adipose-derived MSCs exposed to stretch loading did not show CM gene markers nor spontaneous beating [11]. Bone marrow MSCs treated with stretch could display cardiac gene expressions (e.g., GATA4, Nkx 2.5) but did not form functionally beating CMs [12].…”

Midfacial rejuvenation by hyaluronic acid fillers and subcutaneous adipose tissue – A new concept

“…Mechanical stress is one of the known factors inducing ADMSCs differentiation into muscular or endothelial cells, although short-term mechanical factors alone are not sufficient [42,43]. Deep filler placement, however, results in a prolonged mechanical stress.…”