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。

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。

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。

原始出处：

Cell Stem Cell, Volume 6, Issue 3, 227-237, 5 March 2010 DOI:10.1016/j.stem.2010.01.002

G-CSF Promotes the Proliferation of Developing Cardiomyocytes In Vivo and in Derivation from ESCs and iPSCs

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

Department 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

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.