研究成果：
以干细胞治疗产品研发、干细胞基础与转化医学、细胞衰老等为研究方向，主持国家重点研发计划“干细胞及转化研究”重点专项、国家重点研发计划“发育编程及其代谢调节”重点专项（PI）、国家自然科学基金（7项）、上海市科委重点课题等35项省部级及以上课题，累计经费13555万元。积极参加国家、上海市干细胞研究政策咨询、规划编制、指南撰写与指令性课题。总计发表论文106篇，其中SCI论文79篇，IF合计666。以第一或通讯作者发表SCI论文48篇，IF合计422，21篇IF大于10（其中4篇IF大于20）。申请专利21项，授权13项，申请国际PCT专利1项。参加专著和国家统编教材编写13部。积极参加国家、上海市细胞治疗研究政策咨询，承担细胞治疗与再生医学规划编制、指南撰写与指令性课题。
在干细胞与组织再生、谱系重编程、细胞衰老与肿瘤防治等基础研究方面取得系列重要进展，发表在Nature, Cell Stem Cell, Cell Research, Gastroenterology, Hepatology等国际期刊。1）开展细胞重编程研究，在非供体来源肝细胞获得方面取得突出成绩。率先实现将皮肤成纤维细胞谱系重编程为成熟肝细胞或肝干细胞，实现肝细胞来源选择的重大策略突破（Nature 2011, Cell Stem Cell 2013, Cell Stem Cell 2014）；实现原代肝细胞向肝前体细胞的可逆转化和扩增，解决了原代肝细胞的培养扩增难题，实现肝细胞来源选择新的策略突破（Cell Research 2017, Cell Research 2019a）。2）系统开展肝细胞移植促进肝脏再生的研究，为实现临床转化建立基础。建立肝细胞分离、移植及功能评价的技术方案，建立促进肝细胞移植后在宿主肝脏中的植入和再殖肝脏，建立补片移植技术实现肝干细胞类器官体向肝脏高效移植的策略等（Gastroenterology 2010, Chemical Engineering Journal 2024, Bioactive Materials 2024, Biomaterials 2022, Biomaterials 2021, npj Regenerative Medicine 2023, Matrix Biology 2023, Cell Death & Disease 2014, Cell Death & Disease 2018a, Frontiers in Immunology 2024）。3）建立模拟肝损伤与诱导细胞衰老的研究体系，开展肝细胞衰老与肝癌发生的命运转变研究。发现衰老肝细胞移植后可在宿主肝脏内脱离其衰老表型并获得增殖能力，发现肝细胞损伤程度决定肝细胞走向衰老或发生肝癌的命运转变，通过转染肝细胞核因子实现肝癌细胞逆转为肝细胞样细胞，为肝癌治疗提供了新的治疗策略。构建p21-ATD转基因小鼠模型，可用于示踪、分选和清除p21阳性细胞（Hepatology 2014, Cell Research 2019b, Molecular therapy 2024, Journal of Advanced Research 2024, Clinical and Translational Medicine 2023, Cell Death & Disease 2018b, Frontiers in Immunology 2020, Cell Death & Disease 2020, Cell Death & Disease 2022, Cell Oncol 2022, Frontiers in Immunology 2022）。研究成果被评为中国科学十大进展、细胞出版社中国年度论文等。
在干细胞质量研究、干细胞药物研发等细胞治疗转化方面取得重要进展。建立干细胞体内命运示踪平台，实现非侵入式监测移植细胞的体内命运转归，加速干细胞研究临床转化应用（2019年央视新闻联播《壮丽70年 奋斗新时代——推动高质量发展调研行》专栏报道）。完成“人源肝系细胞体内功能动物模型及相关体系的建立与应用”，对推动人肝系细胞产业化具有重要支撑作用，以第一完成人获上海市优秀发明金奖（2019）、上海市五一劳动奖章（2019）及上海医学科技奖二等奖（2020）。
主持研发多个干细胞治疗新药临床注册研究或干细胞临床备案研究。带领团队开展人羊膜上皮干细胞成药性研究，针对5种适应症获批国家卫健委干细胞临床研究备案项目6项（帕金森病、卵巢早衰、重度宫腔粘连、急性GVHD和急性肾损伤），自主研发Ⅰ类新药“人羊膜上皮干细胞注射液”于2022年2月获批临床试验默示许可（CXSL2101456），并已启动I期临床试验。承担上海市科委重大课题“人脐带来源间充质干细胞的制备及临床前研究”，自主研发Ⅰ类新药“人脐带间充质干细胞注射液” 2024年1月获批临床试验默示许可（CXSL2300728），该项目2022年转让天士力医药集团，转让经费6000万元。
代表性论文：
2024年（待续）
1. Chen MM#, Chen WJ#, Sun SW#, Lu YL, Wu GX, Xu HY, Yang HR, Li C, He WZ, Xu MY, Li XH, Jiang D, Cai YC, Liu CC, Zhang WC, He ZY*. CDK4/6 inhibitor PD-0332991 suppresses hepatocarcinogenesis by inducing senescence of hepatic tumor-initiating cells. Journal of Advanced Research 2024. doi: https://doi.org/10.1016/j.jare.2024.08.034. *Corresponding author. (IF: 11.4，中科院1区)
2. Zhang WC#*, Cui YY#, Lu MQ#, Xu MY#, Li YT#, Song HM, Luo Y, Song JY, Yang Y, Wang XC, Liao LJ, Wang YF, Lola Reid*, He ZY*. Hormonally and Chemically Defined Expansion Conditions for Organoids of Biliary Tree Stem Cells. Bioactive Materials 2024. Published on line. *Corresponding authors. (IF: 18，中科院1区)
3. Chen F, Zhang KS, Wang MJ, He ZY, Yu B, Wang X, Pan XH, Luo YP, Xu SJ, Lau JTY, Han CS, Shi YF, Sun YE, Li SG, Hu YP. VEGF-FGF Signaling Activates Quiescent CD63+ Liver Stem Cells to Proliferate and Differentiate. Adv Sci (Weinh) 2024; e2308711. oi: 10.1002/advs.202308711. (IF: 14.3，中科院1区)
4. Qi YY#, Wang XC#, Bai ZH#, Xu Y, Lu TT, Zhu HY, Zhang SM, Wu ZH, Liu ZM*, He ZY*, Jia WW*. Enhancement of the function of mesenchymal stem cells by using a GMP-grade three-dimensional hypoxic large-scale production system. Heliyon 2024; 10(10), E30968. Published on May 17, DOI: https: //doi.org/10.1016/j.heliyon.2024.e30968. *Corresponding authors. (IF: 3.4)
5. Wang Y#, Yuan T#, Lyu T, Zhang L, Wang M, He ZY*, Wang Y*, Li Z*. Mechanism of inflammatory response and therapeutic effects of stem cell in ischemic stroke: Current evidence and future perspectives. Neural Regeneration Research 2025, 20(1): 67-81. *Corresponding authors. (IF: 5.9)
6. Chen MM#, Wu GX#, Lu YL#, Sun SW, Yu Z, Pan X, Chen WJ, Xu HY, Qiu H, He WZ, Li XH, Wang XC, Luo Y, Du Y, Wu JL, Wei K, Zhang WC, Liu ZM, He ZY *. A p21-ATD Mouse Model for Monitoring and Eliminating Senescent Cells and Its Application in Liver Regeneration post Injury. Molecular Therapy 2024; S1525-0016(24)00218-1. *Corresponding author. (IF: 12.4，中科院1区)
7. Shen SW#, Zhang WC#, Xu C#, Dong ZX, Wang XC, Liu CC, Lu FF, Hu YH, Tang QH*, Cheng Y*, He ZY*. Magnetotactic hepatocytes promote liver repopulation after transplantation. Chemical Engineering Journal 2024; 486, 150278. *Corresponding authors. (IF: 16.744，中科院1区)
8. Wang XC#, Yang C#, Ma XX#, Li XH, Qi YY, Bai ZH, Xu Y, Ma KM, Luo Y, Song JY, Jia WW*, He ZY*, Liu ZM*. Adivision-of-labor mode contributes to the cardioprotective potentia of mesenchyma stem/stromal cells in heart failure post myocardiainfarction. Frontiers in lmmunology 2024; published on line. *Corresponding authors. (IF: 7.3)
9. Aging Biomarker Consortium, Jiang MM#, Zheng ZZ#, Wang X#，Chen YH#，Qu J*，Ding QR*，Zhang WQ*，Liu YS*，Yang JC*，Tang WQ*，Hou YL*，He JH*，Wang L*，Huang PY*，Li LC*，He ZY*，Gao Q*，Lu Q*，Wei L*，Wang YJ*，Ju ZY*，Fan JG*，Ruan XZ*，Guan YF*，Liu GH*，Pei G*，Li J*，Wang YF*. A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement. Life Medicine 2024, lnae004. *Corresponding authors.
10. Wang Y#, Yuan T#, Lyu T, Zhang L, Wang M, He ZY*, Wang Y*, Li Z*. Mechanism of inflammatory response and therapeutic effects of stem cell in ischemic stroke: Current evidence and future perspectives. Neural Regeneration Research 2024; DOI: 10.4103/1673-5374.393104. *Corresponding authors. (IF: 6.058)
2023年
1. He WZ#, Wang XC#, Chen MM#, Li C, Chen WJ, Pan LL, Cui YY, Yu Z, Wu GX, Yang Y, Xu MY, Dong ZX, Ma KM, Wang JH, He ZY*. Metformin reduces hepatocarcinogenesis by inducing downregulation of Cyp26a1 and CD8+ T cells. Clinical and Translational Medicine, 2023; 13(11): e1465. *Corresponding author. (IF: 10.60，中科院1区)
2. Zhang WC#, Xu YM#, Wang CX#, Oikawa T, Su GW, Wauthier E, Wu GX, Sethupathy P, He ZY*, Liu L*, Reid LM*. Fibrolamellar Carcinomas Growth arrested by paracrine signals complexed with synthesized 3-O sulfated heparan sulfate oligosaccharides. Matrix Biology 2023; 121: 194-216. *Corresponding authors. (IF: 6.9，中科院1区)
3. Zhang WC#, Cui YY#, Du Y#, Yang Y#, Fang T#, Lu FF, Kong WX, Xiao CJ, Shi J, Reid LM*, He ZY*. Liver Cell Therapies: Cellular Sources and Grafting Strategies. Frontiers of Medicine 2023; 17(3): 432-457. *Corresponding authors. (IF: 8.1)
4. Zhang WC#, Wang XC#, Lanzoni G, Wauthier E, Simpson S, Ezzell JA, Allen A, Suitt C, Krolik J, Jhirad A, Dominguez-Bendala J, Cardinale V, Alvaro D, Overi D, Gaudio E, Sethupathy P*, Carpino G*, Adin C*, Piedrahita JA*, Mathews K, He ZY*, Reid LM*. A postnatal network of co-hepato/pancreatic stem/progenitors in the biliary trees of pigs and humans. NPJ Regenerative Medicine 2023; 8(1): 40. *Corresponding authors. (IF: 7.2，中科院1区)
5. Yang Y#, Zhang W#, Wang X, Yang J, Cui Y, Song H, Li W, Li W, Wu L, Du Y, He ZY*, Shi J*, Zhang J*. A passage-dependent network for estimating the in vitro senescence of mesenchymal stromal/stem cells using microarray, bulk and single cell RNA sequencing. Frontiers in Cell and Developmental Biology. 2023; 11: 998666. *Corresponding authors. (IF: 5.5)
2022年
1. Chen WJ, Zhang WC, Chen MM, Yang C, Fang T, Wang HF, Reid LM, He ZY*. Applications and mechanisms of the cyclin-dependent kinase 4/6 inhibitor, PD-0332991, in solid tumors. Cell Oncol (Dordr). 2022; 45(6): 1053-1071. *Corresponding author. (IF: 6.6)
2. Zhang WC, Carpino G, Wangensteen KJ, Yan HX, He ZY. Editorial: Cell therapy, liver diseases, and regeneration. Frontiers in Cell and Developmental Biology 2022; 10:999305.
3. Zhang WC, Wauthier E, Lanzoni G, Hani H, Yi XW, Overi D, Shi L, Simpson S, Allen A, Suitt C, Ezzell JA, Alvaro D, Cardinale V, Gaudio E, Carpino G, Prestwich G, Dominguez-Bendala J, Gerber D, Matthews K, Piedrahita J, Adin C, Sethupathy P*, He ZY*, Reid LM*. Patch grafting of organoids of stem/progenitors into solid organs can correct genetic-based disease states. Biomaterials 2022; 288: 121647. *Corresponding authors. (IF: 14，中科院1区)
4. Liu P, Wang XJ, Pan LL, Han B*, He ZY*. Prognostic Significance and Immunological Role of FBXO5 in Human Cancers: A Systematic Pan-Cancer Analysis. Frontiers in Immunology 2022; 901784. *Corresponding authors. (IF: 8.786).
5. Du Y, Zhang WC, Qiu H, Xiao CJ, Shi J, Reid LM, He ZY*. Mouse Models of Liver Parenchyma Injuries and Regeneration. Frontiers in Cell and Developmental Biology 2022; 10: 903740. *Corresponding author. (IF: 6.081)
6. Zhang WC, Lou YR, Zhou JJ, He ZY. Editorial: Stem Cells in Tissue Homeostasis and Disease. Frontiers in Cell and Developmental Biology 2022; 10: 876060.
7. Cai YC#, Fu Y#, Liu CC#, Wang XC#, You P, Li XH, Song YX, Mu XN, Jiang D, Yang Y, Gu YY, Zhang HB*, He ZY*. Stathmin 1 is a biomarker for diagnosis of microvascular invasion to predict prognosis of early hepatocellular carcinoma. Cell Death & Disease 2022; 13(2): 176. *Corresponding authors. (IF: 9).
2021年
1. Zhang WC, Lanzoni G, Hani H, Diletta O, Cardinale V, Simpson S, Pitman W, Allen A, Yi XW, Wang XC, Gerber D, Prestwich G, Lozoya O, Gaudio E, Alvaro D, Tokaz D, Dominguez-Bendala J, Adin C, Piedrahita J, Matthews K, Sethupathy P*, Carpino G, He ZY*, Wauthier E*, Reid LM*. Patch Grafting, Strategies for Transplantation of Organoids into Solid Organs such as Liver. Biomaterials 2021; 277:121067. *Corresponding authors. (IF: 15.304，中科院1区)
2. Lu FF#, Pan X#, Zhang WC#, Su X, Gu YY, Qiu H, Shen SW, Liu CC, Liu W, Zhan ZZ, Liu ZM*, He ZY*. A Three-dimensional Imaging Method for the Quantification and Localization of Dynamic Cell Tracking Post-transplantation. Frontiers in Cell and Developmental Biology 2021; 9: 698795. *Corresponding authors. (IF: 6.081)
3. Wang SS#, Jiang K#, Du XY, Lu YL, Liao LJ, He ZY*, He WZ*. Translational Attenuation Mechanism of ErmB Induction by Erythromycin Is Dependent on Two Leader Peptides. Frontiers in Microbiology 2021; 12: 609711. *Corresponding authors. (IF: 6.064)
4. Wang XC#, Zhang WC#, Yang Y, Wang JS, Qiu H, Liao LJ, Oikawa T, Wauthier E, Sethupathy P, Reid LM, Liu ZM*, He ZY*. A MicroRNA-Based Network Provides Potential Predictive Signatures and Reveals the Crucial Role of PI3K/AKT Signaling for Hepatic Lineage Maturation. Frontiers in Cell and Developmental Biology 2021; 9: 670059. *Corresponding authors. (IF: 6.081).
2020年
1. Liu P#, Tang QH#, Chen MM, Chen WJ, Lu YL, Liu ZM*, He ZY*. Hepatocellular senescence: immunosurveillance and future senescence-induced therapy in hepatocellular carcinoma. Frontiers in Oncology 2020; 10: 589908. *Corresponding authors. (IF: 6.244).
2. Liu W#, Liu Q#, Zhang BL, Lin ZB, Li X, Yang XS, Pu M, Zou RZ, He ZY*, Wang F*, Dou KF*. The mRNA of TCTP functions as a sponge to maintain homeostasis of TCTP protein levels in hepatocellular carcinoma. Cell Death & Disease 2020; 11(11): 974. *Corresponding authors. (IF: 8.469).
2019年
3. Lu ZF#*, Li XH#, Xu YF, Chen MM, Chen W, Chen T, Tang QH*, He ZY*. microRNA-17 functions as an oncogene by down-regulating Smad3 expression in hepatocellular carcinoma. Cell Death & Disease 2019; 10(10):723. *Corresponding authors. (IF: 6.304).
4. Fu YB, He ZY*, Zhang C*. Advances of Stem Cell Therapy to Treat Heart Failure. Nano Life 2019; 9(3): 1941002. *Corresponding authors.
5. Cheng Z#, He ZY#, Cai YC#, Zhang C#, Fu GB, Li HY, Sun W, Liu CC, Cui XL, Ning BF, Xiang DM, Zhou TF, Li XF, Xie WF, Wang HY*, Ding J*. Conversion of hepatoma cells to hepatocyte-like cells by defined hepatocyte nuclear factors. Cell Research 2019; 29(2): 124-135. #Co-first authors. (IF: 20.507，中科院1区).
6. Fu GB#, Zhou X#, Zeng M#, Huang WJ#, Wu HP#, Liu CC, Wu H, Weng J, Zhang HD, Cai YC, Ashton C, Ding M, Tang D, Zhang BH, Gao Y, Yu WF, Zhai B*, He ZY*, Wang HY*, Yan HY*. Expansion and differentiation of human hepatocyte-derived liver progenitor-like cells for the study of hepatotropic pathogen. Cell Research 2019; 29(1): 8-22. *Corresponding authors. (IF: 20.507，中科院1区).
2018年
1. Li XH#, Yang Y#, Liu W, Chen WJ, Hu KY, Wang WY, Wang C, Wu YF, Liu ZM*, He ZY*. Nanomaterials in liver regeneration: the prospect for application. Nano Life 2018; 8(4): 1841005. *Corresponding authors.
2. Yang Y#, Li XH#, Liu W, Chen JW, Liu CC, Cai YC, Song YX, Tang QH, Zhang C*, He ZY*. Generation of hepatocyte-like cells by different strategies for liver regeneration. Nano Life 2018; 8(4): 1841004. *Corresponding authors.
3. Wang C#, Chen WJ#, You P#, Wu YF#, Zheng SY, Liu CC, Xiang D，Wang MJ#, Cai YC, Zhao QH, Borjigin U, Liu W, Xiong WJ, Wangensteen KJ, Wang X, Liu ZM*, He ZY*. The extent of liver injury determines hepatocyte fate toward senescence or cancer. Cell Death & Disease 2018; 9(5): 575. *Corresponding authors. (IF: 5.959).
4. Wang MJ#, Chen F#, Liu QG#, Liu CC, Yao H, Yu B, Zhang HB, Yan HX, Ye YB, Chen T, Wangensteen KJ, Wang X, Hu YP*, He ZY*. Insulin-like growth factor 2 is a key mitogen driving liver repopulation in mice. Cell Death & Disease 2018; 9(2): 26. *Corresponding authors. (IF: 5.959).
5. Xiao MC#, Chen WJ#, Wang C#, Wu YF, Zhu SW, Zeng CY, Cai YC, Liu CC, He ZY*. Senescence and cell death in chronic liver injury: roles and mechanisms underlying hepatocarcinogenesis. Oncotarget 2017; 9(9): 8772-8784. *Corresponding author. (IF: 5.168).
2017年及之前
1. Wu H#, Zhou X#, Fu GB#, He ZY#, Wu HP#, You P, Ashton C, Wang X, Wang HY, Yan HY. Reversible transition between hepatocytes and liver progenitors for in vitro hepatocyte expansion. Cell Research 2017; 27(5): 709-712. #Co-first authors. (IF: 15.606，中科院1区).
2. Zhao H#, He ZY#, Huang DD, Gao J, Gong YF, Wu HY, Xu AF, Meng XJ, Li ZS. Infusion of bone marrow mesenchymal stem cells attenuates experimental severe acute pancreatitis in rats. Stem Cells International 2016; 2016: 7174319. #Co-first authors. (IF: 3.540).
3. Xiang D#, Liu CC#, Wang MJ#, Li JX, Chen F, Yao H, Yu B, Lu L, Borjigin U, Zhong L, Wangensteen KJ, He ZY*, Wang X*, Hu YP*. Non-viral FoxM1 gene delivery to hepatocytes enhances liver repopulation. Cell Death & Disease 2014; 5(5): e1252. *Corresponding authors. (IF: 5.014).
4. Wang MJ#, Chen F#, Li JX, Liu CC, ZhangHB, Xia Y, Yu B, You P, Xiang D, Lu L, Yao H, Borjigin U, Yang GS, Wangensteen KJ, He ZY*, Wang X*, Hu YP*. Reversal of hepatocytes senescence after continuous in vivo cell proliferation. Hepatology 2014, 60(1):349-61. *Corresponding authors. (IF: 11.055，中科院1区).
5. Huang PY#, Zhang LD#, Gao YM#, He ZY#, Yao D, Wu ZT, Cen J, Chen XT, Liu CC, Hu YP, Lai DM, Hu ZL, Chen L, Zhang Y, Cheng X, Ma XJ, Pan GY, Wang X, Hui LJ. Direct reprogramming of human fibroblasts to functional and expandable hepatocyte cells. Cell Stem Cell 2014; 14(3): 370-84. #Co-first authors. (IF: 22.268，中科院1区).
6. Yu B#, He ZY#, You P, Han QW, Xiang D, Chen F, Wang MJ, Liu CC, Lin XW, Borjigin U, Zi XY, Li JX, Zhu HY, Li WL, Han CS, Wangensteen KJ, Shi YF, Hui LJ, Wang X, Hu YP. Reprogramming fibroblasts into bipotential hepatic stem cells by defined factors. Cell Stem Cell 2013; 13(3): 328-340. #Co-first authors. (IF: 22.151，中科院1区).
7. Deng L#, Ke X#, He ZY#, Yang D, Gong H, Zhang Y, Jing X, Yao J, Chen J. A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer. International Journal of Nanomedicine 2012; 7: 5053–5065. #Co-first authors. (IF: 3.463).
8. He ZY, Deng L, Li YF, Xiang D, Hu JK, Chen YX, Wang MJ, Chen F, Liu CC, Li WL, Zi XY, Wu X, Li GP, Wangensteen KJ, Hu YP, Wang X. Murine Embryonic Stem Cell-derived Hepatocytes Correct Metabolic Liver Disease after Serial Liver Repopulation. The International Journal of Biochemistry & Cell Biology 2012; 44(4): 648-58. (IF: 4.152)
9. Huang PY, He ZY, Ji SY, Sun HW, Xiang D, Liu CC, Hu YP, Wang X, Hui LJ. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 2011; 475: 386-389. (IF: 36.280，中科院1区)
10. Su BL#, Liu CC#, Xiang D, Zhang HB, Yuan SM, Wang MJ, Chen F, Zhu HY, He ZY*, Wang X, Hu YP*. Xeno-liver repopulation of human hepatocyte in Fah-/-Nod/Scid mice. Sci China Life Sci 2011; 54(3): 227-234. *Corresponding authors. (IF: 2.024)
11. Li FM#, He ZY#, Li YF, Liu PY, Chen F, Wang MJ, Zhu HY, Ding XY, Wangensteen KJ, Hu YP, Wang X. Combined Activin A/LiCl/Noggin treatment improves production of mouse embryonic stem cell-derived definitive endoderm cells. Journal of Cellular Biochemistry 2011; 112(4): 1022-34. #Co-first authors. (IF: 2.868).
12. Li FM, Liu PY, Liu CC, Xiang D, Deng L, Li WL, Wangensteen KJ, Song JG, Ma Y, Hui LJ, Wei LX, Li LS, Ding XY, Hu YP, He ZY*, Wang X*. Hepatoblast-like progenitor cells derived from embryonic stem cells can repopulate livers of mice. Gastroenterology 2010; 139(6): 2158-2169.e8. *Corresponding authors. (IF: 12.032，中科院1区)
13. He ZY, Zhang HB, Zhang X, Xie DF, Chen YX, Wangensteen KJ, Ekker SC, Firpo M, Liu CC, Xiang D, Zi XY, Hui LJ, Yang GS, Ding XY, Hu YP, Wang X. Liver Xeno-Repopulation with Human Hepatocytes in Fah-/-Rag2-/- Mice after Pharmacological Immunosuppression. American Journal of Pathology 2010; 177(3): 1311-9. (IF: 5.224)
