Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart.
Arodent cardiac side population cell fraction formed clonal spheroids in serum-free medium, which expressed nestin, Musashi-1, and multi-drug resistance transporter gene 1, markers of undifferentiated neural precursor cells. These markers were lost following differentiation, and were replaced by the expression of neuron-, glial-, smooth muscle cell-, or cardiomyocyte-specific proteins. Cardiosphere-derived cells transplanted into chick embryos migrated to the truncus arteriosus and cardiac outflow tract and contributed to dorsal root ganglia, spinal nerves, and aortic smooth muscle cells. Lineage studies using double transgenic mice encoding protein 0-Cre/Floxed-EGFP revealed undifferentiated and differentiated neural crest-derived cells in the fetal myocardium. Undifferentiated cells expressed GATA-binding protein 4 and nestin, but not actinin, whereas the differentiated cells were identified as cardiomyocytes. These results suggest that cardiac neural crest-derived cells migrate into the heart, remain there as dormant multipotent stem cells-and under the right conditions-differentiate into cardiomyocytes and typical neural crest-derived cells, including neurons, glia, and smooth muscle.
Tomita
Yuichi
Y
Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo, Japan.
Matsumura
Keisuke
K
Wakamatsu
Yoshio
Y
Matsuzaki
Yumi
Y
Shibuya
Isao
I
Kawaguchi
Haruko
H
Ieda
Masaki
M
Kanakubo
Sachiko
S
Shimazaki
Takuya
T
Ogawa
Satoshi
S
Osumi
Noriko
N
Okano
Hideyuki
H
Fukuda
Keiichi
K
D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000032:analysis / Q000096:biosynthesis; D002319:Cardiovascular System / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D002465:Cell Movement; D002478:Cells, Cultured; D002642:Chick Embryo; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology; D051379:Mice; D008813:Mice, Inbred ICR; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000637:transplantation*; D009206:Myocardium / Q000737:chemistry / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000637:transplantation*; D009432:Neural Crest / Q000166:cytology / Q000637:transplantation*; D010525:Peripheral Nerves / Q000737:chemistry / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar
D000943:Antigens, Differentiation