2013年9月15日訊 /生物谷BIOON/--西班牙國立癌症研究中心(Spanish National Cancer Research Centre,CNIO)的科學家首次在成體動物的活組織中製造具有胚胎幹細胞特性的成體細胞。科學家也發現這類直接從器官中分離的胚胎幹細胞比從培養細胞體系中得到的幹細胞分化能力更高。特別是這類細胞具有分化全能型,這一特性在培養細胞是無法達到的。
該研究由CNIO的Manuel Serrano博士領導完成。相關報導發表在近期Nature雜誌上。
2006年Shinya Yamanaka博士領導的研究團隊首次在體外建立了胚胎幹細胞,為再生醫學開闢了新的天地。CNIO科學家更進一步,不需要經過細胞培養這一步就直接能夠得到胚胎幹細胞。
CNIO科學家的第一個挑戰是在活體動物中重複Yamanaka的實驗。他們選擇小鼠作為模式動物,採用遺傳操作技術,創建了Yamanaka使用的四個基因的轉基因小鼠。科學家發現這些基因激活能夠使得多個組織和器官中的成體細胞具有胚胎幹細胞的特徵。
該文章的第一作者María Abad稱,在自然情況下發育過程的轉變之前從未被發現過,我們的實驗結果表明不僅在培養體系,在動物器官中同樣也能獲得胚胎幹細胞。
相比於培養體系產生的胚胎幹細胞,CNIO科學家獲得的幹細胞看起來發育狀態更早,具有更大的分化全能型。
科學家甚至在小鼠胸腔和腹腔中誘導產生胚胎類似結構。該胚胎類似結構有胚胎典型的三層結構(外胚層,中胚層,內胚層)。胚外結構如卵黃囊膜甚至有血細胞形成跡象。
科學家強調說,將現在的結果應用於臨床還有一定的距離,但是毋庸置疑的是,這研究對幹細胞研究領域,再生醫學領域和組織工程領域的貢獻是巨大的。(生物谷Bioon.com)
Reprogramming in vivo produces teratomas and iPS cells with totipotency features
María Abad, Lluc Mosteiro, Cristina Pantoja, Marta Canamero, Teresa Rayon, Inmaculada Ors, Osvaldo Grana, Diego Megías, Orlando Domínguez, Dolores Martínez, Miguel Manzanares, Sagrario Ortega & Manuel Serrano.
Reprogramming of adult cells to generate induced pluripotent stem cells (iPS cells) has opened new therapeutic opportunities; however, little is known about the possibility of in vivo reprogramming within tissues. Here we show that transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs, implying that full reprogramming can occur in vivo. Analyses of the stomach, intestine, pancreas and kidney reveal groups of dedifferentiated cells that express the pluripotency marker NANOG, indicative of in situ reprogramming. By bone marrow transplantation, we demonstrate that haematopoietic cells can also be reprogrammed in vivo. Notably, reprogrammable mice present circulating iPS cells in the blood and, at the transcriptome level, these in vivo generated iPS cells are closer to embryonic stem cells (ES cells) than standard in vitro generated iPS cells. Moreover, in vivo iPS cells efficiently contribute to the trophectoderm lineage, suggesting that they achieve a more plastic or primitive state than ES cells. Finally, intraperitoneal injection of in vivo iPS cells generates embryo-like structures that express embryonic and extraembryonic markers. We conclude that reprogramming in vivo is feasible and confers totipotency features absent in standard iPS or ES cells. These discoveries could be relevant for future applications of reprogramming in regenerative medicine.