title: Microgravity potentiates stem cell proliferation while sustaining the capability of differentiation.
abstract: A three-dimensional (3D) clinostat is a device for generating multidirectional G force, resulting in an environment with an average of 10(3) G. Here we report that human mesenchymal stem cells (hMSCs) cultured in a 3D-clinostat (group CL) showed marked proliferation (13-fold in a week) compared with cells cultured under normal conditions of 1 G (group C) (4-fold in a week). Flow cytometry revealed a 6-fold increase in the number of hMSCs double-positive for CD44/CD29 or CD90/CD29 in group CL after 7 days in culture, compared with group C. Telomere length remained the same in cells from both groups during culturing. Group C cells showed increasing expression levels of type II collagen and aggrecan over the culture period, whereas group CL cells showed a decrease to undetectable levels. Pellets of hMSCs from each group were explanted into cartilagedefective mice. The transplants from group CL formed hyaline cartilage after 7 days, whereas the transplants from group C formed only noncartilage tissue containing a small number of cells. These results show that hMSCs cultured in a 3D-clinostat possess the strong proliferative characteristic of stem cells and retain their ability to differentiate into hyaline cartilage after transplantation. On the contrary, cells cultured in a 1-G environment do not maintain these features. Simulated microgravity may thus provide an environment to successfully expand stem cell populations in vitro without culture supplements that can adversely affect stem cell-derived transplantations. This method has significant potential for regenerative medicine and developmental biology.
authors.affiliation: Division of Bio-Environment Adaptation Sciences, Graduate School of Health Sciences, Hiroshima University, Kasumi, Hiroshima, Japan. ryuge@hiroshima-u.ac.jp
authors.forename: Louis
authors.initials: L
authors.lastname: Yuge
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Kajiume
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tahara
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kawahara
authors.forename: Chika
authors.initials: C
authors.lastname: Umeda
authors.forename: Reiko
authors.initials: R
authors.lastname: Yoshimoto
authors.forename: Shu-Liang
authors.initials: SL
authors.lastname: Wu
authors.forename: Kazuko
authors.initials: K
authors.lastname: Yamaoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
authors.forename: Katsuko
authors.initials: K
authors.lastname: Kataoka
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ide
mesh_terms: D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D014893:Weightlessness