5月12日,，國際學(xué)術(shù)期刊《自然》在線發(fā)表了中國科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所惠利健研究小組關(guān)于轉(zhuǎn)化型肝臟細(xì)胞的研究成果，證明肝臟以外的體細(xì)胞可以被誘導(dǎo)直接轉(zhuǎn)化為肝臟細(xì)胞,，為將來從病人自身體細(xì)胞誘導(dǎo)獲得肝臟細(xì)胞進(jìn)行移植的應(yīng)用奠定了基礎(chǔ),。
人體的皮膚、血液,、神經(jīng),、肝臟等終末分化的功能細(xì)胞是由多能干細(xì)胞分化而來，在自然界,，這個(gè)過程是不可逆的,，但從理論來看，通過生物工程它是可逆的,?？茖W(xué)家已通過實(shí)驗(yàn)方法將皮膚細(xì)胞轉(zhuǎn)化為多能干細(xì)胞，然后又把多能干細(xì)胞分化為肝臟細(xì)胞,。而該研究則簡化了這一過程,，將小鼠尾巴上的皮膚成纖維細(xì)胞直接誘導(dǎo)為肝臟細(xì)胞，這種細(xì)胞具有和體內(nèi)肝臟細(xì)胞類似的上皮細(xì)胞形態(tài),、基因表達(dá)譜,、且獲得了肝臟細(xì)胞的功能。
研究所通過實(shí)驗(yàn)發(fā)現(xiàn),，將轉(zhuǎn)化型肝臟細(xì)胞移植于肝衰竭的小鼠,，有近一半仍然存活，證明了轉(zhuǎn)化型肝臟細(xì)胞具有體內(nèi)功能,。據(jù)悉,，該項(xiàng)研究尚處于動(dòng)物實(shí)驗(yàn)階段，應(yīng)用于臨床,，還需要相當(dāng)長時(shí)間優(yōu)化,。
《自然》雜志的編委和評(píng)審專家高度評(píng)價(jià)此項(xiàng)工作的開創(chuàng)性意義，他們認(rèn)為研究中所建立的技術(shù)體系,，作為一項(xiàng)重大突破,，對(duì)同領(lǐng)域的研究工作具有指導(dǎo)意義。
除了在細(xì)胞移植的臨床應(yīng)用前景外,，轉(zhuǎn)化型肝臟細(xì)胞在制藥工業(yè)有關(guān)的藥物代謝和藥物毒理研究中,，在基礎(chǔ)醫(yī)學(xué)和臨床醫(yī)學(xué)中對(duì)肝臟疾病機(jī)理研究也具有廣泛的應(yīng)用前景,。目前已申請了相關(guān)專利，并有意投入開發(fā)利用,，爭取將實(shí)驗(yàn)室的基礎(chǔ)研究成果轉(zhuǎn)化為真正的科研生產(chǎn)力,，回報(bào)社會(huì)，造福人類,。這一工作得到了科技部,、國家自然科學(xué)基金委、中國科學(xué)院的經(jīng)費(fèi)支持,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature DOI： doi:10.1038/nature10116
Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors
Pengyu Huang; Zhiying He; Shuyi Ji; Huawang Sun; Dao Xiang; Changcheng Liu; Yiping Hu; Xin Wang; Lijian Hui
The generation of functional hepatocytes independent of donor liver organs is of great therapeutic interest with regard to regenerative medicine and possible cures for liver disease1. Induced hepatic differentiation has been achieved previously using embryonic stem cells or induced pluripotent stem cells2, 3, 4, 5, 6, 7, 8. Particularly, hepatocytes generated from a patient’s own induced pluripotent stem cells could theoretically avoid immunological rejection. However, the induction of hepatocytes from induced pluripotent stem cells is a complicated process that would probably be replaced with the arrival of improved technology. Overexpression of lineage-specific transcription factors directly converts terminally differentiated cells into some other lineages9, 10, 11, 12, including neurons13, cardiomyocytes14 and blood progenitors15; however, it remains unclear whether these lineage-converted cells could repair damaged tissues in vivo. Here we demonstrate the direct induction of functional hepatocyte-like (iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4, Hnf1α and Foxa3, and inactivation of p19Arf. iHep cells show typical epithelial morphology, express hepatic genes and acquire hepatocyte functions. Notably, transplanted iHep cells repopulate the livers of fumarylacetoacetate-hydrolase-deficient (Fah?/?) mice and rescue almost half of recipients from death by restoring liver functions. Our study provides a novel strategy to generate functional hepatocyte-like cells for the purpose of liver engineering and regenerative medicine.
