title: Distinct qualitative differences between normal and abnormal hemopoietic stem cells in vivo and in vitro.
abstract: The transplantation of partially purified hemopoietic stem cells (HSCs) plus the engraftment of bone from autoimmune-prone mice ((NZW x BXSB)F1 (W/BF1) mice) induces autoimmune diseases in major histocompatibility complex (MHC)-incompatible normal C3H/HeN mice. In contrast, W/BF1 mice die of infection or anemia within three weeks due to a failure in hemopoietic reconstitution when the mice receive partially purified HSCs plus bones from normal C3H/HeN mice, although they survive more than a year without showing any symptoms of autoimmune diseases when they receive T cell-depleted bone marrow cells (without bone grafts) from normal mice. This finding suggests that abnormal HSCs can proliferate even in MHC-incompatible microenvironments, while normal HSCs cannot. This is confirmed by spleen colony-forming assays (CFU-S) on day 12, using pluripotent HSCs (P-HSCs). The P-HSCs of old (> 4 mo) W/BF1 mice (after the development of autoimmune diseases) form high CFU-S counts on day 12 even in the allogeneic C3H environment, although the P-HSCs of normal mice form high CFU-S counts only in the MHC-compatible environments. In addition, abnormal P-HSCs of autoimmune-prone mice can proliferate in vitro in collaboration with MHC-incompatible stromal cells, although normal HSCs do so in collaboration with MHC-compatible stromal cells, but not MHC-incompatible stromal cells. These findings indicate that abnormal P-HSCs are more "resilient" than normal P-HSCs.
authors.affiliation: First Department of Pathology, Kansai Medical University, Moriguchi-City, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kawamura
authors.forename: H
authors.initials: H
authors.lastname: Hisha
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Fukuhara
authors.forename: S
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology