Cardiomyogenic potential of mesenchymal progenitors derived from human circulating CD14+ monocytes.
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 micro-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.
Kodama
Hiroaki
H
Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan.
Inoue
Takafumi
T
Watanabe
Ryuichi
R
Yasuoka
Hidekata
H
Kawakami
Yutaka
Y
Ogawa
Satoshi
S
Ikeda
Yasuo
Y
Mikoshiba
Katsuhiko
K
Kuwana
Masataka
M
D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D018920:Coculture Techniques; D004594:Electrophysiology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000032:analysis
D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D014157:Transcription Factors