日本研究人员日前宣布,他们开发出了利用实验鼠的诱导多能干细胞(iPS细胞)高效制造造血干细胞的技术。医生未来在治疗白血病时,有望利用这种技术制造大量造血干细胞,从而代替骨髓移植。
造血干细胞位于骨髓中,可以分化为红细胞和白细胞。东京都临床医学综合研究所与大阪大学的研究人员利用iPS细胞先制作出了中胚层细胞。这种细胞可以发育为血管和肌肉等组织。随后研究人员向中胚层细胞植入LhX2基因,最终生成了大量的造血干细胞。
研究人员接下来用放射线照射实验鼠,使其失去造血功能,再将用上述方法得到的造血干细胞移植到一部分实验鼠体内。结果显示,和没有接受造血干细胞移植的实验鼠相比,接受移植的实验鼠寿命大幅延长,生存了4个月。
研究人员指出,此前利用iPS细胞培养造血干细胞时,难以单纯生成造血干细胞,还会混杂其他细胞,而这次开发出的新技术使造血干细胞的生成效率达到了原有方法的四五倍。
目前在对白血病患者进行治疗时,主要是移植与患者血液类型接近的正常人骨髓,以利用其中的造血干细胞,帮助患者恢复。研究人员希望在确认安全性后,将这种新技术用于人类的白血病治疗。相关论文已刊登在新一期美国《血液》杂志网络版上。(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.