title: Human cord blood--derived cells generate insulin-producing cells in vivo.
abstract: Here we report the capacity of human cord blood (CB)-derived cells to generate insulin-producing cells. To investigate in vivo capacity of human CB-derived cells, T cell-depleted mononuclear cells were intravenously transplanted into nonobese diabetic/severe combined immunodeficient/beta2-microglobulinnull mice within 48 hours of birth. At 1-2 months post-transplantation, immunofluorescence staining for insulin and fluorescence in situ hybridization (FISH) analysis using a human chromosome probe indicated that human CB-derived cells generated insulin-producing cells at a frequency of 0.65%+/-0.64% in xenogeneic hosts. Reverse transcription-polymerase chain reaction analysis confirmed the transcription of human insulin in the pancreatic tissue of the recipient mice. To clarify the mechanism underlying CB-derived insulin-producing cells, double FISH analysis using species-specific probes was performed. Almost equal proportions of human chromosome+ murine chromosome- insulin+ cells and human chromosome+ murine chromosome+ insulin+ cells were present in recipient pancreatic islets. Taken together, human CB contains progenitor cells, which can generate insulin-producing cells in recipient pancreatic tissues across a xenogeneic histocompatibility barrier by fusion-dependent and -independent mechanisms.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Shuro
authors.initials: S
authors.lastname: Yoshida
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ishikawa
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kawano
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimoda
authors.forename: Seiho
authors.initials: S
authors.lastname: Nagafuchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimoda
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kanemaru
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous
chemical_list: D007328:Insulin