Establishment of a xenograft model of human myelodysplastic syndromes

Yukari Muguruma, Hiromichi Matsushita, Takashi Yahata, Shizu Yumino, Yumiko Tanaka, Hayato Miyachi, Yoshiaki Ogawa, Hiroshi Kawada, Mamoru Ito, Kiyoshi Ando

研究成果: Article査読

29 被引用数 (Scopus)

抄録

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. Design and Methods: Bone marrow CD34+ cells obtained from patients were injected, with or without human mes-enchymal stem cells, into the bone marrow of non-obese diabetic/severe combined immuno-deficient/IL2Rγnull 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 neo-plastic 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.

本文言語English
ページ(範囲)543-551
ページ数9
ジャーナルHaematologica
96
4
DOI
出版ステータスPublished - 2011 4月
外部発表はい

ASJC Scopus subject areas

  • 血液学

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