Hanna Jacob, Wernig Marius, Markoulaki Styliani, Sun Chiao-Wang, Meissner Alexander, Cassady John P, Beard Caroline, Brambrink Tobias, Wu Li-Chen, Townes Tim M, Jaenisch Rudolf
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Science. 2007 Dec 21;318(5858):1920-3. doi: 10.1126/science.1152092. Epub 2007 Dec 6.
It has recently been demonstrated that mouse and human fibroblasts can be reprogrammed into an embryonic stem cell-like state by introducing combinations of four transcription factors. However, the therapeutic potential of such induced pluripotent stem (iPS) cells remained undefined. By using a humanized sickle cell anemia mouse model, we show that mice can be rescued after transplantation with hematopoietic progenitors obtained in vitro from autologous iPS cells. This was achieved after correction of the human sickle hemoglobin allele by gene-specific targeting. Our results provide proof of principle for using transcription factor-induced reprogramming combined with gene and cell therapy for disease treatment in mice. The problems associated with using retroviruses and oncogenes for reprogramming need to be resolved before iPS cells can be considered for human therapy.
最近有研究表明，通过导入四种转录因子的组合，小鼠和人类成纤维细胞可以被重编程为胚胎干细胞样状态。然而，这种诱导多能干细胞（iPS细胞）的治疗潜力仍不明确。通过使用人源化镰状细胞贫血小鼠模型，我们发现，用从自体iPS细胞体外获得的造血祖细胞进行移植后，小鼠能够得到救治。这是在通过基因特异性靶向纠正人类镰状血红蛋白等位基因后实现的。我们的结果为在小鼠疾病治疗中使用转录因子诱导重编程并结合基因和细胞疗法提供了原理证明。在考虑将iPS细胞用于人类治疗之前，需要解决与使用逆转录病毒和癌基因进行重编程相关的问题。
