The Effects of Mechanical Stress on the Growth, Differentiation, and Paracrine Factor Production of Cardiac Stem Cells

Hiroshi Kurazumi,Yoshihiro Takemoto,Masayuki Kubo,Ryo Suzuki,Shigeru Ikenaga,Tao-Sheng Li,Koichi Udo,Akihito Mikamo,Kimikazu Hamano,Mako Ohshima,Yumi Yamamoto,Paul Mcneil

doi:10.1371/journal.pone.0028890

Hiroshi Kurazumi, Yoshihiro Takemoto + Show 10 more

Open Access

https://doi.org/10.1371/journal.pone.0028890

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Journal: PloS one	Publication Date: Dec 28, 2011
Citations: 82	License type: CC BY 4.0

Affiliation: Yamaguchi University, Nagasaki University

Abstract

Stem cell therapies have been clinically employed to repair the injured heart, and cardiac stem cells are thought to be one of the most potent stem cell candidates. The beating heart is characterized by dynamic mechanical stresses, which may have a significant impact on stem cell therapy. The purpose of this study is to investigate how mechanical stress affects the growth and differentiation of cardiac stem cells and their release of paracrine factors. In this study, human cardiac stem cells were seeded in a silicon chamber and mechanical stress was then induced by cyclic stretch stimulation (60 cycles/min with 120% elongation). Cells grown in non-stretched silicon chambers were used as controls. Our result revealed that mechanical stretching significantly reduced the total number of surviving cells, decreased Ki-67-positive cells, and increased TUNEL-positive cells in the stretched group 24 hrs after stretching, as compared to the control group. Interestingly, mechanical stretching significantly increased the release of the inflammatory cytokines IL-6 and IL-1β as well as the angiogenic growth factors VEGF and bFGF from the cells in 12 hrs. Furthermore, mechanical stretching significantly reduced the percentage of c-kit-positive stem cells, but increased the expressions of cardiac troponin-I and smooth muscle actin in cells 3 days after stretching. Using a traditional stretching model, we demonstrated that mechanical stress suppressed the growth and proliferation of cardiac stem cells, enhanced their release of inflammatory cytokines and angiogenic factors, and improved their myogenic differentiation. The development of this in vitro approach may help elucidate the complex mechanisms of stem cell therapy for heart failure.

Highlights

In the past decade, many studies have provided evidence of the potential for cardiac tissue self-regeneration, even in adult mammals and human beings [1,2,3,4,5]
By using an in vitro stretching model, we clearly demonstrated that mechanical stress affects cardiac stem cells in the following ways: (1) stretch inhibited cell growth by suppressing cell proliferation and increasing cell apoptosis, (2) stretch increased the production of inflammatory cytokines and angiogenic growth factors, (3) stretch improved the expression of markers for cardiomyocytes and smooth muscle cells, and (4) stretch enhanced the expression of adhesion molecules
There is increasing evidence that stem cell-based myocardial repair occurs through both direct regeneration and indirect mechanisms [7,8,9]

Summary

Introduction

Many studies have provided evidence of the potential for cardiac tissue self-regeneration, even in adult mammals and human beings [1,2,3,4,5]. This evidence includes a reservoir of cardiac-specific stem cells or progenitor cells found in adult hearts and the increased proliferative activity of cardiomyocytes in failing hearts [1,2,3,4,5]. The implantation of exogenous stem cells is still considering as a promising therapy for heart failure, the mechanism on stem cell therapy have been recently demonstrated to largely depend on paracrine effects rather than direct regeneration of new functional myocardium [7,8,9].

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