Research Article
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Published Online: 24 January 2006

Cardiomyogenic Potential of Mesenchymal Progenitors Derived from Human Circulating CD14+ Monocytes

Publication: Stem Cells and Development
Volume 14, Issue Number 6

Abstract

Previously, we reported a unique CD14+CD45+CD34+type I collagen+ cell fraction derived from human circulating CD14+ monocytes, named monocyte-derived mesenchymal progenitors (MOMPs). These primitive cells differentiate along mesenchymal lineages, including bone, cartilage, fat, and skeletal muscle. Here, we demonstrate that CD14+ monocytes generate MOMPs that differentiate into cardiomyocytes. MOMPs labeled with a fluorescent marker and co-cultivated with rat cardiomyocytes for 4 weeks expressed the cardiomyocyte-specific transcription factors Nkx2.5, GATA-4, eHAND, and MEF2 and the hematopoietic/monocytic markers CD45 and CD14 within 10 days and retained their proliferative capacity for up to 16 days. A subpopulation of MOMPs subsequently expressed the cardiomyocyte-specific markers µ-sarcomeric actinin, troponin I, and atrial natriuretic peptide on day 21. Furthermore, fluorescence-labeled, spontaneously beating cells that formed gap junctions with adjacent rat cardiomyocytes appeared in these cultures and these cells exhibited electrophysiological properties typical of ventricular myocytes. The co-cultivation of human MOMPs with rat GFP-tagged cardiomyocytes resulted in the generation of human cardiomyocytes lacking green fluorescent protein (GFP) staining, suggesting that our observations could not solely be explained by cell fusion. Our results demonstrate for the first time that human circulating CD14+ monocytes include progenitors capable of proliferating and differentiating along the cardiomyogenic lineage via their differentiation into MOMPs.

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cover image Stem Cells and Development
Stem Cells and Development
Volume 14Issue Number 6December 2005
Pages: 676 - 686
PubMed: 16433623

History

Published online: 24 January 2006
Published in print: December 2005

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Hiroaki Kodama
Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan.
Takafumi Inoue
Department of Basic Medical Sciences, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Ryuichi Watanabe
Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan.
Hidekata Yasuoka
Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan.
Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
Yutaka Kawakami
Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan.
Satoshi Ogawa
Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
Yasuo Ikeda
Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
Katsuhiko Mikoshiba
Department of Basic Medical Sciences, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Dr. Masataka Kuwana
Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan.

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