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關(guān)鍵技術(shù)里程碑

2012
2012

成功獲得小鼠iNSCs,,并證實(shí)其與野生型神經(jīng)干細(xì)胞具備相似的表型和分化能力,;


2012
2012

重編程小鼠成纖維細(xì)胞獲得iNSCs

2013
2013

成功證明了表達(dá)膠質(zhì)細(xì)胞來源神經(jīng)營養(yǎng)因子GDNF的自體骨髓間充質(zhì)干細(xì)胞(BMMSCs)對非人靈長類PD模型具有保護(hù)作用,。

2015
2015

成功完成了自體iPSCs獲得的多巴胺能神經(jīng)元移植治療非人靈長類PD模型的工作,并證明其安全有效,。

2015
2015

世界上首次從理論上證明了iNSCs對PD模型動物具有治療作用。

2015
2015

成功利用iPSCs技術(shù)建立了研究家系遺傳神經(jīng)退行性疾病的細(xì)胞模型,。世界首次將病人和健康人的iPSCs細(xì)胞系分化為成熟的小腦浦肯野神經(jīng)元,,為后續(xù)研究II型小腦共濟(jì)失調(diào)的細(xì)胞學(xué)機(jī)制建立了細(xì)胞模型。

2016
2016

成功將成人外周血單個核細(xì)胞誘導(dǎo)為人誘導(dǎo)神經(jīng)干細(xì)胞(hiNSCs),。取材更簡單,、安全,患者接受度更高

2018
2018

人類外周血單個核細(xì)胞定向分化為iNSC-DAP,,移植PD小鼠模型獲得有效性數(shù)據(jù)

2022
2022

iNSC-DAP治療PD靈長類研究獲得有效數(shù)據(jù),,啟動國內(nèi)首個IIT臨床研究

2023
2023

7月18日,全球首例使用iNSC-DAP自體細(xì)胞移植治療帕金森病的神經(jīng)外科手術(shù)在首都醫(yī)科大學(xué)宣武醫(yī)院成功完成

2024
2024

宣武醫(yī)院首例自體誘導(dǎo)神經(jīng)干細(xì)胞來源的多巴胺能神經(jīng)前體細(xì)胞治療帕金森病患者隨訪一年取得安全性和有效性

  • 2012
  • 2012
  • 2013
  • 2015
  • 2015
  • 2015
  • 2016
  • 2018
  • 2022
  • 2023
  • 2024

1.Chen Z *, Phillips LK, Gould E, Campisi J, Lee SW, Ormerod BK, Zwierzchoniewska M, Martinez O, Palmer TD *. MHC Mismatch Inhibits Neurogenesis and Neuron Maturation in Stem Cell Allografts. PLoS ONE. 2011 March 6(3): e14787 (IF= 3.24) citation: 36 

2.Chen Z * and YA Zhang.  A glimpse of stem cell research in China. Progress in Biochemistry and Biophysics. 2011/38 :11 PP.1011-1014.  (IF=0.351) 

3.Ren Z, Wang J, Zhu W, Guan Y, Zou C, Chen Z *, Zhang YA *. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro. Exp Cell Res. 2011 Dec 10;317(20):2950-7.  (IF=3.905) citation: 59

4.Du Q, Guan Y, Ji H, Chen Z, Zhang YA. Effect of monolayer cells on sphere cells - two types of cells that emerge during the neural differentiation of mouse embryonic stem cells. Neuroscience Letters. 2011 Oct 31;504(3):285-9. (IF=3.046) citation: 4

5.Sheng C#, Zheng Q#, Wu J#, Xu Z, Wang L, Li W, Zhang H, Zhao XY, Liu L, Wang Z, Guo C, Wu HJ, Liu Z, Wang L, He S, Wang XJ, Chen Z * and Zhou Q *. Direct Reprogramming of Sertoli Cells into Multipotent Neural Stem Cells by Defined Factors. Cell Research. 2012 Jan;22(1):208-18. (IF=25.617) citation: 146  

6.Ren Z, Zhang YA *, Chen Z *. Spontaneous transformation of cynomolgus mesenchymal stem cells in vitro: further confirmation by short tandem repeat analysis. Exp Cell Res. 2012 March 10; 318(5):435-440. (IF=3.905) citation: 14

7.Sheng C#, Zheng Q#, Wu J#, Xu Z, Sang L, Wang L, Guo C, Zhu W, Tong M, Liu L, Zhao XY, Wang L, Chen Z * and Zhou Q *. Generation of dopaminergic neurons directly from mouse fibroblasts and fibroblast-derived neural progenitors. Cell Research. 2012 Apr;22(4):769-72. (IF=25.617) citation: 50

8.Zou C, Wang J, Wang S, Huang F, Ren Z, Chen Z, Zhang YA. Characterization of Induction of Diabetes in Juvenile Cynomolgus Monkeys with Different doses of Streptozotocin. SCIENCE CHINA Life Sciences. 2012 Mar;55(3):210-8. (IF=6.038) citation: 14

9.Chen Z * and Palmer TD *. Differential roles of TNFR1 and TNFR2 signaling in adult hippocampal neurogenesis. Brain Behav Immun. 2013 May;30:45-53. (IF=7.217) citation: 100

10.Ren Z, Wang J, Wang S, Zou C, Li X, Guan Y, Chen Z *, Zhang YA *. Autologous transplantation of GDNF-expressing mesenchymal stem cells protects against MPTP-induced damage in cynomolgus monkeys. Scientific Reports. 2013 Sep 27;3:2786. doi: 10.1038/srep02786. (IF= 4.379) citation: 24

11.Chen Z*, Zhang Y*.Introduction to the special topic "stem cells and regenerative medicine". Sci China Life Sci. 2014 Jun;57(6):561-3. (IF=6.038) citation: 2

12.Wu J, Sheng C, Liu Z, Jia W, Wang B, Li M, Fu L, ren Z, An J, Sang L, Song G, Wu Y, Xu Y, Wang S, Chen Z, Zhou Q, Zhang YA. Lmx1a enhances the effect of iNSCs in a PD model. Stem Cell Research. 2015, 14, 1-9. (IF=2.020) 24

13.Chen Z*. Cell therapy for Parkinson’s disease: new hope from reprogramming technologies. Aging and Disease. 2015 Nov 17;6(6):499-503. (IF=6.745) citation: 16

14.Chen Z*, Zhang YA*. Cell therapy for macular degeneration – first phase I/II pluripotent stem cell-based clinical trial shows promise. Sci China Life Sci. 2015 Jan; 58(1):1-2. (IF=6.038) citation: 10

15.Wang S, Wang B, Pan N, Fu L, Wang C, Song G, An J, Liu Z, Zhu W, Guan Y, Xu ZQD, Chan P, Chen Z*, Zhang YA. Differentiation of human induced pluripotent stem cells to mature functional Purkinje neurons. Scientific Reports. 2015 Mar 18;5:9232. (IF=4.379) citation: 65

16.Wang S#, Zou C#, Fu L, Wang B, An J, Song G, Wu J, Tang X, Li M, Zhang J, Yue F, Zheng C, Chan P, Zhang YA, Chen Z*. Autologous iPSC-derived dopamine neuron transplantation in a nonhuman primate Parkinson’s disease model. Cell Discovery. (2015) 1, 15012;  doi:10.1038/celldisc.2015.12,,(IF=10.849) citation: 32

17.Comparison of intracerebral transplantation effects of different stem cells on rodent stroke models. Wu Y, Wu J, Ju R, Chen Z, Xu Q. Cell Biochem Funct. 2015 Jun;33(4):174-82. (IF=3.685) citation: 19

18.Duan S, Yuan G, Liu X, Ren R, Li J, Zhang W, Wu J, Xu X, Fu L, Li Y, Yang J, Zhang W, Bai R, Yi F, Suzuki K, Gao H, Esteban CR, Zhang C, Izpisua Belmonte JC, Chen Z, Wang X, Jiang T, Qu J, Tang F, Liu GH.  PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype.  Nature  Communications. 2015 Dec 3;6:10068. (IF=14.919) citation: 105

19.Tang X, Wang S, Bai Y, Wu J, Fu L, Li M, Xu Q, Xu ZQD, Zhang YA *, Chen Z *. Conversion of adult human peripheral blood mononuclear cells into neural stem cell by using episomal vectors. Stem Cell Research. 2016 Jan 15;16(2):236-242. (IF=2.020) citation: 23

20.Da Y*, Wang W, Liu Z, Chen H, Di L, Previch L, Chen Z*. Aberrant trafficking of a Leu89Pro connexin32 mutant associated with X-linked dominant Charcot-Marie-Tooth disease. Neurological Research. 2016 Oct;38(10):897-902. (IF=2.448) citation: 3

21.Li P#, Li M#, Tang X, Wang S, Zhang YA*, Chen Z*. Accelerated generation of oligodendrocyte progenitor cells from human induced pluripotent stem cells by forced expression of Sox10 and Olig2. Sci China Life Sci. 2016 Nov;59(11):1131-1138. (IF= 6.038) citation: 13

22.Zou C, Lu Y, Teng X, Wang S, Sun X, Huang F, Shu G, Huang X, Guo H, Chen Z, Zhang J, Zhang YA. MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys. Sci Rep. 2017 May 31;7(1):2505. (IF=4.379) citation: 2

23.Shuyan Wang#, Zhongfeng Liu#, Yanxia Ye#, Bingnan Li, Tiantian Liu, Weiqi Zhang, Guang-Hui Liu, Y. Alex Zhang, Jing Qu*, Dawei Xu*, Zhiguo Chen*. Ectopic hTERT expression facilitates reprograming of fibroblasts derived from patients with Werner syndrome as a WS cellular model. Cell Death and Disease, 2018 Sep 11;9(9):923. (IF=8.469) citation: 8 PMID: 30206203

24.Yanpeng Yuan, Xihe Tang, Yun-Fei Bai, Shuyan Wang, Jing An, Yanchuan Wu, Zhi-Qing David Xu,  Y. Alex Zhang*, Zhiguo Chen*. Dopaminergic neurons differentiated from human blood-derived induced neural stem cells show efficacy in a mouse Parkinson’s disease model. Theranostics, 2018; 8(17):4679-4694. doi:10.7150/thno.26643. (IF=11.556) citation: 7  PMID: 30279731

25.Yunqian Guan#, Xiaobo Li#, Wenxiu Yu#, Zhaohui Liang, Min Huang, Renchao Zhao, Chunsong Zhao, Yao  Liu, Haiqiang Zou, Yanli Hao, Zhiguo Chen*. Intravenous transplantation of mesenchymal stem cells reduces the number of infiltrated Ly6C+ cells but enhances the proportions positive for BDNF, TNF-1 and IL-1 in the infarct cortices of dMCAO rats. Stem Cell International, 2018 Oct 2;2018:9207678. doi: 10.1155/2018/9207678. (IF=5.443) citation: 9  PMID:30405724

26.Wei Zheng, Qian Li, Chao Zhao, Yuwei Da, Hong-Liang Zhang*, Zhiguo Chen*. Differentiation of Glial Cells from hiPSCs: Potential Applications in Neurological Diseases and Cell Replacement Therapy. Front. Cell. Neurosci., 2018 Aug 8;12:239. doi: 10.3389/fncel.2018.00239. (IF=5.505) citation: 21  PMID: 30140204

27.Weiqi Zhang, Haifeng Wan, Guihai Feng, Jing Qu, Jiaqiang Wang, Yaobin Jing, Ruotong Ren,Zunpeng Liu, Linlin Zhang, Zhiguo Chen, Shuyan Wang, Yong Zhao, Zhaoxia Wang, Yun Yuan, Qi Zhou, Wei Li, Guang-Hui Liu & Baoyang Hu. SIRT6 deficiency results in developmental retardation in cynomolgus monkeys. Nature. 2018. Aug;560(7720):661-665. doi.org/10.1038/s41586-018-0437-z. (IF=49.962) citation: 71

28.Li M, Wang Y, Zhang J, Cao Z, Wang S, Zheng W, Li Q, Zheng T, Wang X, Xu Q, Chen Z*. Culture of pyramidal neural precursors, neural stem cells, and fibroblasts on various biomaterials. J Biomater Sci Polym Ed. 2018 Dec;29(17):2168-2186. doi: 10.1080/09205063.2018.1528520. (IF=3.517) citation: 1 PMID:30261158

29.Zhongfeng Liu, Xuan Wang, Kewen Jiang, Y. Alex Zhang*, Zhiguo Chen*. TNF??-induced Up-regulation of Ascl2 Affects the Differentiation and Proliferation of Neural Stem Cells. Aging and Disease. 2019 Dec; 10(6):1207-1220. doi:10.14336/AD.2018.1028. (IF=6.745) citation: 6  PMID:31788333

30. Zheng W,  Chen Z*. Generation of induced neural stem cells from peripheral mononuclear cells and differentiation toward DA neuron precursors for transplantation studies. JoVE, 2019 Jul 11;(149). doi: 10.3791/59690. (IF=1.355) citation: 1  PMID:31355797

31.Jing Y, Yang D, Bai F, Zhang C, Qin C, Li D,,Wang L, Yang M, Chen Z, Li J. Melatonin treatment alleviates spinal cord injury-induced gut dysbiosis in mice. J Neurotrauma. 2019 Sep 15;36(18):2646-2664. (IF= 5.269) citation: 10

32.Liu S, Chen Z*, Employing endogenous NSCs to promote recovery of spinal cord injury. Stem Cells International, 2019 May 5;2019:1958631. (IF=5.443) citation: 16 PMID:31191666

33.Zhao Y#, Liu Z#, Wang X#, Wu H, Zhang J, Yang J, Zhang F, Liu L, Long J*, Lu P*, Chen Z*. Treatment with Humanized Selective CD19CAR-T Cells Shows Efficacy in Highly Treated B-ALL Patients Who Have Relapsed after Receiving Murine-Based CD19CAR-T Therapies. Clin Cancer Res. 2019 Sep 15;25(18):5595-5607. (IF=12.531) citation: 7  PMID:31300451 

34.Cai R, Zhang Y, Simmering JE, Schultz JL, Li Y, Fernandez-Carasa I, Consiglio A, Raya A, Polgreen PM, Narayanan NS, Yuan Y, Chen Z, Su W, Han Y, Zhao C, Gao L, Ji X, Welsh MJ, Liu L. Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases. J Clin Invest. 2019 Sep 16. pii: 129987. doi: 10.1172/JCI129987. (IF=14.808) citation: 32

35.Chi H, Guan Y, Li F, Chen Z*. The Effect of Human Umbilical Cord Mesenchymal Stromal Cells in Protection of Dopaminergic Neurons from Apoptosis by Reducing Oxidative Stress in the Early Stage of a 6-OHDA-Induced Parkinson's Disease Model. Cell Transplant. 2019 Dec;28(1_suppl):87S-99S. (IF=4.064) citation: 8  PMID:31775521

36.Lei L, Shen XM, Wang SY, Lu Y, Wang SB, Chen H, Liu Z, Ouyang YS, Duo JY, Da YW*, Chen ZG, Presence of antibodies against low-density lipoprotein receptor-related protein 4 and impairment of neuromuscular junction in a Chinese cohort of amyotrophic lateral sclerosis. Chin Med J (Engl). 2019 Jun 20;132(12):1487-1489. (IF=2.628) 

37.Han D, Zheng W, Wang X, Chen Z*. Proteostasis of α-Synuclein and Its Role in the Pathogenesis of Parkinson's Disease. Front Cell Neurosci. 2020 Mar 10;14:45. doi: 10.3389/fncel.2020.00045. eCollection 2020. (IF=5.505) citation: 4  PMID:32210767

38.Lei L, Chen H, Lu Y, Zhu W, Ouyang Y, Duo J, Chen Z*, Da Y*. Unusual electrophysiological findings in a Chinese ALS 4 family with SETX-L389S mutation: a three-year follow-up. J Neurol. 2021 Mar;268(3):1050-1058. doi: 10.1007/s00415-020-10246-2. Epub 2020 Sep 30. (IF=4.849) citation: 3

39.Li X#, Yu W#, Guan Y#, Zou H, Liang Z, Huang M, Zhao R, Zhao C, Ren Z, Chen Z*. Peripheral Circulation and Astrocytes Contribute to the MSC-Mediated Increase in IGF-1 Levels in the Infarct Cortex in a dMCAO Rat Model. Stem Cells Int. 2020 Sep 1; 2020:8853444. (IF=5.443)  PMID:32952570 citation: 1

40.Han D#, Zheng X#, Wang X#, Jin T, Cui L*, Chen Z*. Mesenchymal Stem/Stromal Cell-Mediated Mitochondrial Transfer and the Therapeutic Potential in Treatment of Neurological Diseases. Stem Cells Int. 2020 Jul 7;2020:8838046.  (IF=5.443)  citation: 3  PMID:32724315

41.Kai Wang#, Yu Zhao#, Xuan Wang#, Bin Wang, Maoquan Qin, Guanghua Zhu, Huantong Wu, Zhongfeng Liu, Xueling Zheng, Huyong Zheng*, Zhiguo Chen*. Humanized selective CD19CAR-T treatment induces MRD-negative remission in a pediatric B-ALL patient with primary resistance to murine-based CD19CAR-T therapy. Frontiers in Immunology.  December 23, 2020 | https://doi.org/10.3389/fimmu.2020.581116. (IF= 7.561)   PMID:33424835

42.Yingli Jing#; Yan Yu*; Fan Bai#; Limiao Wang; Degang Yang; Chao Zhang; Chuan Qin; Mingliang Yang; Dong Zhang; Yanbing Zhu; Jianjun Li*; Zhiguo Chen*. Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis. Microbiome. 2021 Mar 7;9(1):59. doi: 10.1186/s40168-021-01007-y. (IF=14.650) PMID: 33678185  citation: 12

43.Guan Y#, Wang R#, Li X, Zou H, Yu W, Liang Z, Li L, Chen L, Zhou L*, Chen Z*. Astrocytes constitute the major TNF-α-producing cell population in the infarct cortex in dMCAO rats receiving intravenous MSC infusion. Biomed Pharmacother. 2021 Oct;142:111971. doi: 10.1016/j.biopha.2021.111971. Epub 2021 Jul 31.(IF=7.419)citation: 1

44.Li M, Zhang HP, Wang XY, Chen ZG, Lin XF, Zhu W. Mesenchymal Stem Cell-Derived Exosomes Ameliorate Dermal Fibrosis in a Murine Model of Bleomycin-Induced Scleroderma. Stem Cells Dev. 2021 Oct 1;30(19):981-990. (IF=4.390)

45.Liu B#, Li M#, Zhang L*, Chen Z*, Lu P*. Motor neuron replacement therapy for amyotrophic lateral sclerosis. Neural Regen Res. 2022 Aug;17(8):1633-1639. doi: 10.4103/1673-5374.332123. (IF=5.135).

46.Jing Y, Bai F, Wang L, Yang D, Yan Y, Wang Q, Zhu Y, Yu Y*, Chen Z*. Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site. Microbiol Spectr. 2022 Apr 25:e0017722. (IF=9.043) PMID: 35467388

47.Liang Y, Li S, Li Y, Li M, Sun X, An J, Xu Q, Chen Z, Wang Y. Impact of hydrogel stiffness on the induced neural stem. cells modulation. Ann Transl Med. 2021 Dec;9(24):1784. doi: 10.21037/atm-21-6189. (IF=3.616)

48.Yu Zhao#, Jianping Zhang#, Junfang Yang#, Huantong Wu#, Yao Chen#,Nannan Li, Zhongfeng Liu, Xuan Wang, Weihua Liu, Guangji Zhang, Bin-Bing Stephen Zhou*, Peihua Lu* and Zhiguo Chen*. Long-Term Safety and Efficacy of CD19 Humanized Selective CAR-T Therapy in B-ALL Patients Who Have Previously Received Murine-Based CD19 CAR-T Therapy. Front. Oncol., 21 June 2022. https://doi.org/10.3389/fonc.2022.884782. (IF=6.244)

49.Fengyan Li, Aixia Zhang, Mo Li, Xueyao Wang, Xuan Wang, Yunqian Guan, Jing An, Deqiang Han, Y. Alex Zhang*, Zhiguo Chen*. Induced neural stem cells from Macaca fascicularis show potential of dopaminergic neuron specification and efficacy in a mouse Parkinson’s disease model. Acta Histochemica 124 (2022) 151927. (IF=2.479)

50.Zhou L, Wang X, Wang X, An J, Zheng X, Han D, Chen Z*. Neuroprotective effects of human umbilical cord mesenchymal stromal cells in PD mice via centrally and peripherally suppressing NLRP3 inflammasome-mediated inflammatory responses. Biomed Pharmacother. 2022 Sep;153:113535. (IF=7.419)

51.Mengjia Li, Zhengbo Wang, Tianqi Zheng, Tianzhuang Huang, Baoguo Liu, Deqiang 5 Han, Sumei Liu, Bochao Liu, Mo Li, Wei Si, Y. Alex Zhang*, Yuyu Niu*, Zhiguo Chen*. Characterization of human induced neural stem cells and derivatives following transplantation into the central nervous system of a nonhuman primate and rats. Stem Cells Int 2022 Dec 28;2022:1396735. (IF=5.443)

52.Zhou L, Han D, Wang X, Chen Z*. Probiotic Formulation VSL#3 Interacts with Mesenchymal Stromal Cells To Protect Dopaminergic Neurons via Centrally and Peripherally Suppressing NOD-Like Receptor Protein 3 Inflammasome-Mediated Inflammation in Parkinson's Disease Mice. Microbiol Spectr. 2023 Feb 2:e0320822. (IF=9.043)

53.Xin Zheng#, Deqiang Han#, Weihua Liu, Xueyao Wang, Na Pan, Yuping Wang, Zhiguo Chen*. Human iPSC-derived midbrain organoids functionally integrate into striatum circuits and restore motor function in a mouse model of Parkinson's disease. Theranostics 2023; 13(8): 2673-2692. (IF=11.6)

54.Wang L#, Wang X#, Chen Q, Wei Z, Xu X, Han D, Zhang Y, Chen Z*, Liang Q*. MicroRNAs of extracellular vesicles derived from mesenchymal stromal cells alleviate inflammation in dry eye disease by targeting the IRAK1/TAB2/NF-κB pathway. Ocul Surf. 2023 Mar 27;28:131-140. (IF=6.268)

55.Zhang G, Zhao Y, Liu Z, Liu W, Wu H, Wang X, Chen Z*. GD2 CAR-T cells in combination with Nivolumab exhibit enhanced antitumor efficacy. Transl Oncol. 2023 Jun;32:101663. (IF=4.803)

56.Zhang Q, Chen Z, Zhang K, Zhu J, Jin T. FGF/FGFR system in the central nervous system demyelinating disease: Recent progress and implications for multiple sclerosis. CNS Neurosci Ther. 2023 Mar 16. (IF=7.035)


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