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Published online
doi:10.1083/jcb.200603014
The Journal of Cell Biology, Vol. 176, No. 3, 329-341
The Rockefeller University Press, 0021-9525 $30.00
© Oyama et al.
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Article

Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo



Tomomi Oyama1, Toshio Nagai1, Hiroshi Wada1, Atsuhiko Thomas Naito1, Katsuhisa Matsuura1, Koji Iwanaga1, Toshinao Takahashi1, Motohiro Goto1, Yoko Mikami1, Noritaka Yasuda1, Hiroshi Akazawa1, Akiyoshi Uezumi2, Shin'ichi Takeda3, and Issei Komuro1

1 Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
2 Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
3 Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan

Correspondence to Issei Komuro: komuro-tky{at}umin.ac.jp

Side population (SP) cells, which can be identified by their ability to exclude Hoechst 33342 dye, are one of the candidates for somatic stem cells. Although bone marrow SP cells are known to be long-term repopulating hematopoietic stem cells, there is little information about the characteristics of cardiac SP cells (CSPs). When cultured CSPs from neonatal rat hearts were treated with oxytocin or trichostatin A, some CSPs expressed cardiac-specific genes and proteins and showed spontaneous beating. When green fluorescent protein–positive CSPs were intravenously infused into adult rats, many more (~12-fold) CSPs were migrated and homed in injured heart than in normal heart. CSPs in injured heart differentiated into cardiomyocytes, endothelial cells, or smooth muscle cells (4.4%, 6.7%, and 29% of total CSP-derived cells, respectively). These results suggest that CSPs are intrinsic cardiac stem cells and involved in the regeneration of diseased hearts.

T. Oyama, H. Wada, and T. Nagai contributed equally to this paper.

Abbreviations used in this paper: ANF, atrial natriuretic factor; BMP, bone morphogenetic protein; Brcp, breast cancer resistance protein; CMP, cardiac MP cell; CSP, cardiac SP cell; cTnT, cardiac troponin T; HDAC, histone deacetylases; MDR, multidrug resistance; MEF, myocyte-enhancer factor; MLC, myosin light chain; MP, main population; OT, oxytocin; OTA, OT antagonist; PE, phycoerythrin; PY, Pyronin Y; SA, sarcomeric {alpha}-actinin; Sca-1, stem cell antigen 1; SMA, smooth muscle cell actin; SP, side population; TSA, trichostatin A; vWF, von Willebrand factor.


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