Isoproterenol directs hair follicle-associated pluripotent (HAP) stem cells to differentiate in vitro to cardiac muscle cells which can be induced to form beating heart-muscle tissue sheets.
Nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells are located in the bulge area of the follicle. Previous studies have shown that HAP stem cells can differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. HAP stem cells effected nerve and spinal cord regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. The differentiation potential to cardiac muscle cells was greatest in the upper part of the follicle. The beat rate of the cardiac muscle cells was stimulated by isoproterenol. In the present study, we observed that isoproterenol directs HAP stem cells to differentiate to cardiac muscle cells in large numbers in culture compared to HAP stem cells not supplemented with isoproterenol. The addition of activin A, bone morphogenetic protein 4, and basic fibroblast growth factor, along with isoproternal, induced the cardiac muscle cells to form tissue sheets of beating heart muscle cells. These results demonstrate that HAP stem cells have great potential to form beating cardiac muscle cells in tissue sheets.
a Department of Dermatology , Kitasato University School of Medicine , Minami Ward , Sagamihara , Japan.
Aiko
A
Yamazaki
a Department of Dermatology , Kitasato University School of Medicine , Minami Ward , Sagamihara , Japan.
Masateru
M
Yashiro
a Department of Dermatology , Kitasato University School of Medicine , Minami Ward , Sagamihara , Japan.
Sumiyuki
S
Mii
a Department of Dermatology , Kitasato University School of Medicine , Minami Ward , Sagamihara , Japan.
Ryoichi
R
Aki
a Department of Dermatology , Kitasato University School of Medicine , Minami Ward , Sagamihara , Japan.
Yuko
Y
Hamada
a Department of Dermatology , Kitasato University School of Medicine , Minami Ward , Sagamihara , Japan.
Nobuko
N
Arakawa
b Department of Physiology , Kitasato University School of Medicine , Minami Ward , Sagamihara , Japan.|c Department of Cellular & Molecular Physiology , Kitasato Univ Grad Sch Med Sci , Minami Ward , Sagamihara , Japan.
Katsumasa
K
Kawahara
d AntiCancer, Inc. , San Diego , CA , USA.|e Department of Surgery , University of California San Diego , San Diego , CA USA.
Robert M
RM
Hoffman
a Department of Dermatology , Kitasato University School of Medicine , Minami Ward , Sagamihara , Japan.
Yasuyuki
Y
Amoh
D028341:Activins / Q000502:physiology; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D018859:Hair Follicle / Q000166:cytology; D007545:Isoproterenol / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000502:physiology*
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; C422405:activin A; D016222:Fibroblast Growth Factor 2; D028341:Activins; D007545:Isoproterenol
GFP; activin A; basic fiboblast growth factor; bone morphogenetic protein 4; cardiac muscle cell sheets; differentiation; hair follicle; isoproterenol; nestin; pluripotent; stem cells