title: Differentiation of Mouse Pancreatic Stem Cells Into Insulin-Producing Cells by Recombinant Sendai Virus-Mediated Gene Transfer Technology.
abstract: Islet transplantation, including β-cells, has proven to be effective for diabetes in many recent studies; however, this treatment strategy requires sufficient organ donors. One attractive approach for the generation of β-cells is to utilize the expansion and differentiation of cells from pancreatic stem cells (PSCs), which are closely associated to the β-cells lineage. In this study, we investigated whether important transcription factors (Pdx-1, Ngn3, NeuroD, and MafA) in islet cells could be efficiently transduced into mouse PSCs (mPSCs) using Sendai virus (SeV) vectors and found that the transduced cells were differentiated into insulin-producing pancreatic β-cells. The mPSCs transduced with single transcription factors using SeV vectors could not express the insulin-2 mRNA. When combinations of two transcription factors were transduced using the SeV vectors, including combinations of Pdx-1 + NeuroD, Pdx-1 + MafA, and NeuroD + MafA, the expression of insulin-2 mRNA was low but could be detected. When combinations of three or more transcription factors were transduced using SeV vectors, the expression of insulin-2 mRNA could be detected. In particular, the transduction of the combination of PDX-1, NeuroD, and MafA produced the most effective for the expression of insulin-2 mRNA out of all of the different combinations examined. These data suggest that the transduction of transcription factors using SeV vectors facilitates mPSC differentiation into insulin-producing cells and showed the possibility of regenerating β-cells by using transduced PSCs.
authors.affiliation: Department of Advanced Medicine in Biotechnology and Robotics, Nagoya University Graduate School of Medicine, Higashi-ku, Nagoya, Japan; †FIRST Research Center for Innovative Nanobiodevices, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yukawa
authors.affiliation: ‡ Baylor All Saints Medical Center and Baylor Research Institute , Dallas, TX , USA.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Department of Advanced Medicine in Biotechnology and Robotics, Nagoya University Graduate School of Medicine, Higashi-ku, Nagoya, Japan; §Research Institute of Environmental Medicine, Stress Adaption and Protection, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Oishi
authors.affiliation: Department of Advanced Medicine in Biotechnology and Robotics, Nagoya University Graduate School of Medicine, Higashi-ku, Nagoya, Japan; ¶Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu-shi, Aichi, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: # DNAVEC Corporation , Tsukuba-shi, Ibaragi , Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.affiliation: # DNAVEC Corporation , Tsukuba-shi, Ibaragi , Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Advanced Medicine in Biotechnology and Robotics, Nagoya University Graduate School of Medicine, Higashi-ku, Nagoya, Japan; **The Foundation for Promotion of State of the Art in Medicine and Health Care, Chikusa-ku, Nagoya, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: †FIRST Research Center for Innovative Nanobiodevices, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan; ††Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan; ‡‡Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Hayashi-cho, Takamatsu, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Baba
keywords: Insulin-producing cells; Islet transplantation; Pancreatic stem cells (PSCs); Sendai virus (SeV)