Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells

doi:10.1016/j.bbrc.2008.06.074

Biochemical and Biophysical Research Communications

Volume 374, Issue 1, 12 September 2008, Pages 11-16

https://doi.org/10.1016/j.bbrc.2008.06.074 Get rights and content

Abstract

Mesenchymal stem cells (MSC) transplantation has been proved to be promising strategy to treat the failing heart. The effect of MSC transplantation is thought to be mediated mainly in a paracrine manner. Recent reports have suggested that cardiac progenitor cells (CPC) reside in the heart. In this study, we investigated whether MSC had paracrine effects on CPC in vitro. CPC were isolated from the neonatal rat heart using an explant method. MSC were isolated from the adult rat bone marrow. MSC-derived conditioned medium promoted proliferation of CPC and inhibited apoptosis of CPC induced by hypoxia and serum starvation. Chemotaxis chamber assay demonstrated that MSC-derived conditioned medium enhanced migration of CPC. Furthermore, MSC-derived conditioned medium upregulated expression of cardiomyocyte-related genes in CPC such as β-myosin heavy chain (β-MHC) and atrial natriuretic peptide (ANP). In conclusion, MSC-derived conditioned medium had protective effects on CPC and enhanced their migration and differentiation.

Section snippets

Materials and methods

Isolation and expansion of mesenchymal stem cells from rat bone marrow. All protocols were performed in accordance with the guidelines of the Animal Care Committee of the National Cardiovascular Center Research Institute, Japan. Isolation and expansion of MSC were performed according to previously described methods [2]. In brief, we used 6- to 8-week-old male Lewis rats (Japan SLC, Hamamatsu, Japan) and harvested their bone marrow by flushing the femoral and tibial cavities with

Isolation and features of CPC

One to two weeks after explantation, a layer of fibroblast-like cells from adherent explants was generated, over which small, round, phase-bright cells migrated (Fig. 1A and B). The number of these cells increased gradually, and these CPC could be harvested by washing with PBS from 10 to 14 days after explantation. The morphological features of these cells were similar to those of CPC reported previously [11]. RT-PCR analysis showed that these cells expressed stem cell markers such as c-kit and

Discussion

In the present study, we demonstrated that (1) MSC-derived conditioned medium had protective effects on CPC under hypoxia and serum starvation, (2) MSC-derived conditioned medium enhanced CPC migration, and (3) CPC differentiation into cardiomyocytes phenotype was enhanced by MSC-derived conditioned medium.

Multipotent stem cells have been shown to reside in the heart in several species including rat, mouse, dog and human [9], [10], [11], [12]. Beltrami et al. have reported that c-kit-positive

Acknowledgments

We thank Dr. Masaaki Kawashiri for generous help (Kanazawa University). This work was supported by research grants for Human Genome Tissue Engineering 009 from the Ministry of Health, Labor and Welfare, and the Industrial Technology Research Grant Program of the New Energy and Industrial Technology Development Organization (NEDO) of Japan.

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Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells

Abstract

Section snippets

Materials and methods

Isolation and features of CPC

Discussion

Acknowledgments

Am. J. Cardiol.

Cell

J. Biol. Chem.

Dev. Biol.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Multilineage potential of adult human mesenchymal stem cells

Science

Bone-marrow-derived cells for enhancing collateral development: mechanisms, animal data, and initial clinical experiences

Circ. Res.

Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis

Am. J. Physiol. Heart Circ. Physiol.

Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction

Nat. Med.

Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy

Circulation

Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms

Circulation