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Cell Stem Cell:增加心肌细胞的方法
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8 h( Y" Q$ l; o3 Q: r, t文章来源:新华网 : N+ g3 }. N0 v( N' x$ _& `
日本庆应义塾大学教授福田惠一和助教下地显一郎近日发现,一种名为“粒细胞集落刺激因子”的物质可以帮助心肌细胞大量增殖。4 k3 h- e5 c9 o
" o. }2 @% C+ `! h( H4 H+ {+ B老鼠胎儿在发育初期,心肌细胞会迅速增殖。福田对在母鼠子宫中发育了10天的老鼠胎儿进行了专门研究。他发现,这一时期老鼠胎儿体内的“粒细胞集落刺激因子”数量增加,于是猜测这种因子与心肌细胞增殖相关。6 [$ S4 R; d3 w& Z( C: w
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为了证明这一猜测,福田利用胚胎干细胞技术培育出了猴子的心肌细胞,然后加入“粒细胞集落刺激因子”,结果猴子心肌细胞的数量增加了数十倍。这一成果发表在最新一期美国《细胞—干细胞》(Cell Stem Cell)杂志上。6 C# ]5 l2 u( S$ D
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此前,科学家已经发现,“粒细胞集落刺激因子”可以刺激骨髓产生大量白细胞,用于治疗由化疗导致的白细胞减少。福田指出,这次的成果可能会把“粒细胞集落刺激因子”进一步推向再生医疗的前台。
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原始出处:
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Cell Stem Cell, Volume 6, Issue 3, 227-237, 5 March 2010 DOI:10.1016/j.stem.2010.01.0026 G" q- e8 O) K! F* T* E
- }, E8 Z% g( s; EG-CSF Promotes the Proliferation of Developing Cardiomyocytes In Vivo and in Derivation from ESCs and iPSCs( u( H# ]# v& }& s9 {6 [( A$ c; A9 e
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Kenichiro Shimoji, Shinsuke Yuasa, Takeshi Onizuka, Fumiyuki Hattori, Tomofumi Tanaka, Mie Hara, Yohei Ohno, Hao Chen, Toru Egasgira, Tomohisa Seki, Kojiro Yae, Uichi Koshimizu, Satoshi Ogawa, Keiichi Fukuda
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2 |5 n4 Q0 k! b1 p9 aDepartment of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo 160-8582, Japan Cardiology Division, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan Biomedical Research Laboratories, Asubio Pharma Co., Ltd., Tokyo 618-8513, Japan Corresponding author These authors contributed equally to this work: ?( _. |4 H5 G$ e
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During a screen for humoral factors that promote cardiomyocyte differentiation from embryonic stem cells (ESCs), we found marked elevation of granulocyte colony-stimulating factor receptor (G-CSFR) mRNA in developing cardiomyocytes. We confirmed that both G-CSFR and G-CSF were specifically expressed in embryonic mouse heart at the midgestational stage, and expression levels were maintained throughout embryogenesis. Intrauterine G-CSF administration induced embryonic cardiomyocyte proliferation and caused hyperplasia. In contrast, approximately 50% of csf3r–/– mice died during late embryogenesis because of the thinning of atrioventricular walls. ESC-derived developing cardiomyocytes also strongly expressed G-CSFR. When extrinsic G-CSF was administered to the ESC- and human iPSC-derived cardiomyocytes, it markedly augmented their proliferation. Moreover, G-CSF-neutralizing antibody inhibited their proliferation. These findings indicated that G-CSF is critically involved in cardiomyocyte proliferation during development, and may be used to boost the yield of cardiomyocytes from ESCs for their potential application to regenerative medicine. |
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