日本研究人員日前宣布，他們開發(fā)出了利用實(shí)驗(yàn)鼠的誘導(dǎo)多能干細(xì)胞（iPS細(xì)胞）高效制造造血干細(xì)胞的技術(shù),。醫(yī)生未來在治療白血病時(shí),，有望利用這種技術(shù)制造大量造血干細(xì)胞，從而代替骨髓移植,。
造血干細(xì)胞位于骨髓中,，可以分化為紅細(xì)胞和白細(xì)胞。東京都臨床醫(yī)學(xué)綜合研究所與大阪大學(xué)的研究人員利用iPS細(xì)胞先制作出了中胚層細(xì)胞,。這種細(xì)胞可以發(fā)育為血管和肌肉等組織,。隨后研究人員向中胚層細(xì)胞植入LhX2基因，最終生成了大量的造血干細(xì)胞,。
研究人員接下來用放射線照射實(shí)驗(yàn)鼠,，使其失去造血功能，再將用上述方法得到的造血干細(xì)胞移植到一部分實(shí)驗(yàn)鼠體內(nèi),。結(jié)果顯示，和沒有接受造血干細(xì)胞移植的實(shí)驗(yàn)鼠相比,，接受移植的實(shí)驗(yàn)鼠壽命大幅延長(zhǎng),，生存了4個(gè)月。
研究人員指出,，此前利用iPS細(xì)胞培養(yǎng)造血干細(xì)胞時(shí),，難以單純生成造血干細(xì)胞,，還會(huì)混雜其他細(xì)胞，而這次開發(fā)出的新技術(shù)使造血干細(xì)胞的生成效率達(dá)到了原有方法的四五倍,。
目前在對(duì)白血病患者進(jìn)行治療時(shí),，主要是移植與患者血液類型接近的正常人骨髓，以利用其中的造血干細(xì)胞,，幫助患者恢復(fù),。研究人員希望在確認(rèn)安全性后，將這種新技術(shù)用于人類的白血病治療,。相關(guān)論文已刊登在新一期美國(guó)《血液》雜志網(wǎng)絡(luò)版上,。（生物谷Bioon.com）
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Blood DOI 10.1182/blood-2010-07-298596
In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2
Kenji Kitajima1,*, Ken-ichi Minehata1, Kenji Sakimura2, Toru Nakano3 and Takahiko Hara1
Abstract
Identification of genes involved in in vitro differentiation induction of embryonic stem cells (ESCs) into hematopoietic stem cells (HSCs) has been challenged during last decade. To date, a homeobox transcription factor Hoxb4 has been only demonstrated to possess such an effect in mice. Here, we show that HSC-like cells were efficiently induced from mouse ESCs by enforced expression of Lhx2, a LIM-homeobox transcription factor. Transduction of Lhx2 into ESC-derived mesodermal cells resulted in robust differentiation of c-Kit+/Sca-1+/Lineage- (KSL) cells in vitro. The KSL cell induction frequency was superior to the case of Hoxb4. Furthermore, transplantation of Lhx2-transduced hematopoietic cells into lethally irradiated mice resulted in multi-lineage repopulation of hematopoietic cells over 4 months. Transduction of Lhx2 into induced pluripotent stem cells (iPSCs) was also effective in generating KSL cells in vitro, as well as HSC-like activities in vivo. These results demonstrate that ectopic expression of Lhx2 confers an in vivo engrafting capacity to ESC/iPSC-derived hematopoietic cells and in vivo behavior of iPSC-derived hematopoietic cells is almost identical to that of ESC-derived cells.
