title: Hypoxia Enhances Differentiation of Hair Follicle-Associated-Pluripotent (HAP) Stem Cells to Cardiac-Muscle Cells.
abstract: We have previously demonstrated that the neural stem-cell marker nestin is expressed in hair-follicle stem cells located in the bulge area which are termed hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15-negative and nestin-positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin-expressing stem cells could effect nerve and spinal cord regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. We recently 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. In the present study, we report that, under hypoxic conditions, HAP stem cells differentiated to troponin-positive cardiac-muscle cells at a higher rate that under normoxic conditions. Hypoxia did not influence the differentiation to other cell types. For future use of HAP stem cells for cardiac muscle regeneration, hypoxia should enhance the rate of differentiation thereby providing patients more opportunities to use their own HAP stem cells which are easily accessible, for this purpose. J. Cell. Biochem. 118: 554-558, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine, Minami Ward, Sagamihara, Kanagawa, 252-0374, Japan.|Department of Dermatology, National Hospital Organization Yokohama Medical Center, Totsuka Ward, Yokohama, 245-8575, Japan.
authors.forename: Kyoumi
authors.initials: K
authors.lastname: Shirai
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine, Minami Ward, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hamada
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine, Minami Ward, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Arakawa
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine, Minami Ward, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Yamazaki
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine, Minami Ward, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tohgi
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine, Minami Ward, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Aki
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine, Minami Ward, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Mii
authors.affiliation: AntiCancer, Inc., 7917 Ostrow Street, San Diego, California, 92111.|Department of Surgery, University of California, San Diego, California, 92103.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine, Minami Ward, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Amoh
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D015687:Cell Hypoxia; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*
keywords: CARDIAC MUSCLE CELLS; DIFFERENTIATION; HAIR FOLLICLE; HYPOXIA; NESTIN; PLURIPOTENT; STEM CELL