title: Long-term ex vivo maintenance of testis tissues producing fertile sperm in a microfluidic device.
abstract: In contrast to cell cultures, particularly to cell lines, tissues or organs removed from the body cannot be maintained for long in any culture conditions. Although it is apparent that in vivo regional homeostasis is facilitated by the microvascular system, mimicking such a system ex vivo is difficult and has not been proved effective. Using the culture system of mouse spermatogenesis, we addressed this issue and devised a simple microfluidic device in which a porous membrane separates a tissue from the flowing medium, conceptually imitating the in vivo relationship between the microvascular flow and surrounding tissue. Testis tissues cultured in this device successfully maintained spermatogenesis for 6 months. The produced sperm were functional to generate healthy offspring with micro-insemination. In addition, the tissue kept producing testosterone and responded to stimulation by luteinizing hormone. These data suggest that the microfluidic device successfully created in vivo-like conditions, in which testis tissue maintained its physiologic functions and homeostasis. The present model of the device, therefore, would provide a valuable foundation of future improvement of culture conditions for various tissues and organs, and revolutionize the organ culture method as a whole.
authors.affiliation: Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan.|Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Komeya
authors.affiliation: Department of Mechanical Engineering, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Mechanical Engineering, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan.|Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Yokonishi
authors.affiliation: Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sato
authors.affiliation: Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kojima
authors.affiliation: Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Katagiri
authors.affiliation: Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan.|Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan.|Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sanjo
authors.affiliation: Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yao
authors.affiliation: RIKEN, Bioresource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kamimura
authors.affiliation: RIKEN, Bioresource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Inoue
authors.affiliation: RIKEN, Bioresource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Ogonuki
authors.affiliation: RIKEN, Bioresource Center, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.affiliation: Institute of Industrial Science, University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8505, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Kanagawa 236-0004, Japan.|Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D056656:Lab-On-A-Chip Devices; D008297:Male; D051379:Mice; D046210:Microfluidic Analytical Techniques; D013091:Spermatogenesis; D013094:Spermatozoa / Q000166:cytology*; D013737:Testis / Q000166:cytology* / Q000502:physiology*; D013739:Testosterone / Q000096:biosynthesis; D046509:Tissue Culture Techniques
chemical_list: D013739:Testosterone