演題詳細

一般口演 / Oral Session

一般口演 34 (Oral Session 34) :MDS/MPN:基礎 2

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日程
2013年10月11日(金)
時間
15:25 - 16:25
会場
第14会場 / Room No.14 (札幌市教育文化会館 3F 研修室305)
座長・司会
原田 浩徳 (Hironori Harada):1
1:順天堂大学 血液内科
 
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Search for pathogenesis of acquired myelodysplastic syndromes using reprogramming technology

演題番号 : OS-1-171

蝶名林 和久 (Kazuhisa Chonabayashi):1,2、河原 真大 (Masahiro Kawahara):2、渡辺 亮 (Akira Watanabe):1、沖田 圭介 (Keisuke Okita):1、西澤 正俊 (Masatoshi Nishizawa):1,2、門脇 則光 (Norimitsu Kadowaki):2、高折 晃史 (Akifumi Takaori-Kondo):2、山中 伸弥 (Shinya Yamanaka):1、吉田 善紀 (Yoshinori Yoshida):1

1:Center for iPS Cell Research and Application, Kyoto Univ., Japan、2:Dept. of Hematol. and Oncol., Kyoto Univ., Japan

 

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell diseases characterized by inefficient hematopoiesis and risk of progression to AML with poor prognosis. These diseases remain poorly understood, mainly due to a difficulty in the ex vivo culture of primary MDS cells and a lack of good animal models. Induced pluripotent stem cells (iPSCs) may act as a new platform for elucidation of the pathogenesis of MDS. We used episomal methods to generate iPSCs from blood cells of a MDS patient (RAEB-1 by WHO classification) with isolated 20q deletion. We established more than 30 iPSC lines derived from MDS cells as well as 6 normal iPSC lines derived from T cells (T-iPSC lines) of the same patient. All MDS-iPSC lines had the chromosomal deletion (20q11.2-13.1) identical to those of the primary MDS cells, whereas all T-iPSC lines had normal diploid. MDS-iPSC lines expressed pluripotent stem cell markers at levels comparable to those in T-iPSC lines. All 6 selected MDS-iPSC lines formed teratomas. We assessed hematopoietic differentiation potential of 6 MDS-iPSC lines and 6 isogenic normal T-iPSC lines using OP9 coculture and embryoid body formation. Differentiation into hematopoietic stem cells of MDS-iPSC lines was comparable to that of T-iPSC lines. However, hematopoietic colony formation in methylcellulose culture and further differentiation in erythroid and neutrophil culture were severely impaired in all tested MDS-iPSC lines. This iPSC-based system could be useful for studying the precise molecular mechanisms of MDS and testing new therapeutic compounds.

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