具有高效肝再生能力的原代人肝細胞的體外擴增

2018年12月，同濟大學(xué)醫(yī)學(xué)院上海東方醫(yī)院心律失常教育部重點實驗室；中國科學(xué)院上海生物科學(xué)研究院上海生物化學(xué)與細胞生物學(xué)研究所細胞生物學(xué)國家重點實驗室；上海工業(yè)大學(xué)生命科學(xué)與技術(shù)學(xué)院；復(fù)旦大學(xué)上海醫(yī)學(xué)院腫瘤中心腫瘤科；中國科學(xué)院廣州生物醫(yī)藥衛(wèi)生研究院華南干細胞生物學(xué)與再生醫(yī)學(xué)研究所再生生物學(xué)重點實驗室；干細胞與再生醫(yī)學(xué)創(chuàng)新研究院(Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China；State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China；School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China；Department of Integrative Oncology,   Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College,Fudan University, Shanghai 200032, China；Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China；Stem Cell and Regenerative Medicine Innovation Academy, Beijing 100101, China) Luying Peng老師研究團隊在《Cell Stem Cell》上發(fā)表論文：

“In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity”

“具有高效肝再生能力的原代人肝細胞的體外擴增”

Abstract：

Transplantation of human hepatocytes (HHs) holds significant potential for treating liver diseases. However, the supply of transplantable HHs is severely constrained by limited donor availability and compromised capacity for in vitro expansion. In response to chronic injury, some HHs are reprogrammed into proliferative cells that express both hepatocyte and progenitor markers, suggesting exploitable strategies for expanding HHs in vitro. Here, we report defined medium conditions that allow 10,000-fold expansion of HHs. These proliferating HHs are bi-phenotypic, partially retaining hepatic features while gaining expression of progenitor-associated genes. Importantly, these cells engraft into injured mouse liver at a level comparable to primary HHs, and they undergo maturation following transplantation in vivo or differentiation in vitro. Thus, this study provides a protocol that enables large-scale expansion of transplantable HHs, which could be further developed for modeling and treating human liver disease.

摘要：

人肝細胞移植(HHs)在治療肝臟疾病方面具有重要的潛力。然而，可移植HHs的供應(yīng)受到供體有限和體外擴增能力受損的嚴重限制。在對慢性損傷的反應(yīng)中，一些HHs被重新編程為表達肝細胞和祖細胞標記的增殖細胞，這提示了在體外擴展HHs的可開發(fā)策略。在這里，科研人員報告了允許HHs擴展10,000倍的定義培養(yǎng)基條件。這些增殖的HHs是雙表型的，部分保留肝臟特征，同時獲得祖細胞相關(guān)基因的表達。重要的是，這些細胞以與原發(fā)HHs相當?shù)乃街踩胧軗p小鼠肝臟，并且它們在體內(nèi)移植或體外分化后成熟。因此，本研究提供了一種能夠大規(guī)模擴展可移植HHs的方案，可以進一步開發(fā)用于人類肝臟疾病的建模和治療。

該論文中，L-Wnt3a細胞的體外培養(yǎng)是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯(lián)系北京締一生物400-166-8600.