title: Establishment of a xenograft model of human myelodysplastic syndromes.
abstract: BACKGROUND
  To understand how myelodysplastic syndrome cells evolve from normal stem cells and gain competitive advantages over normal hematopoiesis, we established a murine xenograft model harboring bone marrow cells from patients with myelodysplastic syndromes or acute myeloid leukemia with myelodysplasia-related changes.
  
  
  METHODS
  Bone marrow CD34(+) cells obtained from patients were injected, with or without human mesenchymal stem cells, into the bone marrow of non-obese diabetic/severe combined immunodeficient/IL2Rγ(null) hosts. Engraftment and differentiation of cells derived from the patients were investigated by flow cytometry and immunohistochemical analysis.
  
  
  RESULTS
  Co-injection of patients' cells and human mesenchymal stem cells led to successful engraftment of patient-derived cells that maintained the immunophenotypes and genomic abnormalities of the original patients. Myelodysplastic syndrome-originated clones differentiated into mature neutrophils, megakaryocytes, and erythroblasts. Two of the samples derived from patients with acute myeloid leukemia with myelodysplasia-related changes were able to sustain neoplastic growth into the next generation while these cells had limited differentiation ability in the murine host. The hematopoiesis of mice engrafted with patients' cells was significantly suppressed even when human cells accounted for less than 1% of total marrow mononuclear cells. Histological studies revealed invasion of the endosteal surface by patient-derived CD34(+) cells and disruption of extracellular matrix architecture, which probably caused inhibition of murine hematopoiesis.
  
  
  CONCLUSIONS
  We established murine models of human myelodysplastic syndromes using cells obtained from patients: the presence of neoplastic cells was associated with the suppression of normal host hematopoiesis. The efficiency of engraftment was related to the presence of an abnormality in chromosome 7.
authors.affiliation: Research Center for Regenerative Medicine, Division of Hematopoiesis, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Muguruma
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Matsushita
authors.forename: Takashi
authors.initials: T
authors.lastname: Yahata
authors.forename: Shizu
authors.initials: S
authors.lastname: Yumino
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hayato
authors.initials: H
authors.lastname: Miyachi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawada
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34