鸡胚及禽类细胞系在生物医药领域的应用及研究进展

doi:10.16431/j.cnki.1671-7236.2020.11.043

摘要/Abstract

摘要： 鸡胚因发育过程清楚，长久以来作为基础和应用科学研究领域重要的实验模型，尤其在鸡胚发育早期绒毛尿囊膜阶段，因其血管丰富，是天然的免疫缺陷宿主，是病理学、药理学和肿瘤学等研究领域的理想实验模型。作者简述了发育早期的鸡胚组织结构，并介绍了鸡胚绒毛尿囊膜在肿瘤研究、血管生成、器官移植、烧伤等疾病机理研究中的应用，以及在鸡胚病理模型基础上进行的抗肿瘤药物筛选的应用。重点介绍了鸡胚及禽类细胞系在病毒繁殖和疫苗生产、治疗性蛋白和单抗生产方面的应用研究进展。多种人源病毒、禽源病毒、支原体等可在鸡胚及禽类细胞上增殖，并用于疫苗生产。作者对常用的禽类纤维原细胞和多能干细胞的发展和特点进行了阐述，并总结了商业化的禽类细胞系来源以及部分易感病毒。鸡胚表达系统能够在目的蛋白特定位点产生人源化糖基，减少目的蛋白对人的过敏反应，且禽蛋廉价易得，可作为生产人用单克隆抗体和治疗性蛋白的合适供体。作者介绍了鸡胚及禽类细胞系在生物医药领域应用的最新进展，并对鸡胚作为动物模型在未来的应用进行了展望。

关键词: 鸡胚; 细胞系; 鸡胚绒毛尿囊膜(CAM); 模型

Abstract: Chicken embryo has long been an important experimental model in basic and applied science because of its clear development process,especially in the early development of chicken embryo chorioallantoic membrane stage,due to its abundant blood vessels,it is a natural immunodeficiency host and can be used as an ideal experimental model for pathology,pharmacology and oncology research.The authors briefly described the tissue structure of early stage of chicken embryo,the application of chick embryo chorioallantoic membrane model in tumor,angiogenesis,organ transplantation,burn and other diseases,and the application of anti-cancer drug screening based on the pathological model of chicken embryo.The advances in the application of chicken embryo and avian cell lines in virus reproduction,vaccine production,therapeutic protein production and monoclonal antibody production were reviewed.A variety of human viruses,avian viruses and mycoplasma can proliferate in chicken embryos and avian cell lines and be used in vaccine production.In this paper,the development and characteristics of commonly used avian fibroblasts and pluripotent stem cells were described,and the source of commercial avian cell lines and some susceptible viruses were summarized.Chicken embryo expression system can produce human glycosylates at specific sites of target proteins,reduce the allergic reaction of the target protein to human,and poultry eggs are cheap and easily available,so it can be used as a suitable donor for the production of human monoclonal antibodies and therapeutic proteins.In this paper,the recent progress in the application of chicken embryos and avian cell lines in the field of biomedicine was introduced,and the future application of chicken embryos as animal models was forecasted.

Key words: chicken embryo; cell lines; chick embryo chorioallantoic membrane(CAM); model

中图分类号:

S851.2

王婧, 杨海峰, 王妲妲, 陈晓兰. 鸡胚及禽类细胞系在生物医药领域的应用及研究进展[J]. 中国畜牧兽医, 2020, 47(11): 3783-3791.

WANG Jing, YANG Haifeng, WANG Dada, CHEN Xiaolan. The Application and Research Progress of Chicken Embryo and Avian Cell Lines in Biomedicine[J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(11): 3783-3791.

参考文献

[1] KAIN K H,MILLER J W,JONES-PARIS C R,et al.The chick embryo as an expanding experimental model for cancer and cardiovascular research[J].Developmental Dynamics,2014,243(2):216-228.
[2] 秦瑶,柯逸晖,徐宏景,等.鸡胚尿囊膜模型在化妆品毒性和功效评估中的应用[J].日用化学品科学,2016,39(7):15-20. QIN Y,KE Y H,XU H J,et al.Application of chicken chorioallantoic membrane model in toxicity and efficacy assessment of cosmetics[J].Detergent & Cosmetics,2016,39(7):15-20.(in Chinese)
[3] GOODPASTURE E W,WOODRUFF A M,BUDDINGH G.The cultivation of vaccine and other viruses in the chorioallantoic membrane of chick embryos[J].Science,1931,74(1919):371-372.
[4] COUSSENS P M,SMITH K A,WEBER P S,et al.Immortalized chick embryo cell line adapted to serum-free growth conditions and capable of replicating human and reassortant H5N1 influenza strains for vaccine production[J].Vaccine,2011,29(47):8661-8668.
[5] HORIE M,SASSA Y,IKI H,et al.Isolation of avian bornaviruses from psittacine birds using QT6 quail cells in Japan[J].Journal of Veternary Medicine Science, 2016,78(2):305-308.
[6] CHAN J F,YIP C C,TSANG J O,et al.Differential cell line susceptibility to the emerging Zika virus:Implications for disease pathogenesis,non-vector-borne human transmission and animal reservoirs[J].Emerging Microbes & Infections, 2016,5(8):e93.
[7] AUBRIT F,PERUGI F,LEON A,et al.Cell substrates for the production of viral vaccines[J].Vaccine, 2015,33(44):5905-5912.
[8] WANG B,WANG F,HUANG H,et al.A novel DT40 antibody library for the generation of monoclonal antibodies[J].Virologica Sinica,2019,34(6):641-647.
[9] HERRON L R,PRIDANS C,TURNBULL M L,et al.A chicken bioreactor for efficient production of functional cytokines[J].BMC Biotechnology,2018,18(1):82.
[10] FARZANEH M,HASSANI S N,MOZDZIAK P,et al.Avian embryos and related cell lines:A convenient platform for recombinant proteins and vaccine production[J].Biotechnology Journal,2017,12(5):1600598.
[11] VARGAS A,ZEISSER-LABOUEBE M,LANGE N,et al.The chick embryo and its chorioallantoic membrane (CAM) for the in vivo evaluation of drug delivery systems[J].Advanced Drug Delivery Reviews,2007,59(11):1162-1176.
[12] CIMPEAN A M,RIBATTI D,RAICA M.The chick embryo chorioallantoic membrane as a model to study tumor metastasis[J].Angiogenesis,2008,11(4):311-319.
[13] RIBATTI D.The chick embryo chorioallantoic membrane (CAM).A multifaceted experimental model[J].Mechanisms of Development,2016,141:70-77.
[14] RIBATTI D,TAMMA R.The chick embryo chorioallantoic membrane as an in vivo experimental model to study multiple myeloma[J].Enzymes,2019,46:23-35.
[15] KOMATSU A,HIGASHI Y,MATSUMOTO K.Various CAM tumor models[J].Enzymes,2019,46:37-57.
[16] VALIYLYTE I,CURKUNAVICIUTE R,RIBOKAITE L,et al.The anti-tumorigenic activity of Sema3C in the chick embryo chorioallantoic membrane model[J].Interna-tional Journal of Molcular Sciences, 2019,20(22):5672.
[17] ULUS G,KOPARAL A T,BAYSAL K,et al.The anti-angiogenic potential of (±) gossypol in comparison to suramin[J].Cytotechnology,2018,70(6):1537-1550.
[18] NAIK M,BRAHMA P,DIXIT M.A cost-effective and efficient chick ex-ovo CAM assay protocol to assess angiogenesis[J].Methods and Protocols,2018,1(2):19.
[19] MANGIR N,RAZA A,HAYCOCK J W,et al.An improved in vivo methodology to visualise tumour induced changes in vasculature using the chick chorionic allantoic membrane assay[J].In Vivo,2018,32(3):461-472.
[20] TAIZI M,DEUTSCH V R,LEITNER A,et al.A novel and rapid in vivo system for testing therapeutics on human leukemias[J].Experimental Hematology,2006,34:1698-1708.
[21] SKOWRON M A,SATHE A,ROMANO A,et al.Applying the chicken embryo chorioallantoic membrane assay to study treatment approaches in urothelial carcinoma[J].Urologic Oncology, 2017,35(9):544.e11-544.e23.
[22] DE LUISI A,FERRUCCI A,COLUCCIA AM,et al.Lenalidomide restrains motility and overangiogenic potential of bone marrow endothelial cells in patients with active multiple myeloma[J].Clinical Cancer Research,2011,17(7):1935-1946.
[23] ROCCARO A M,HIDESHIMA T,RICHARDSON P G,et al.Bortezomib as an antitumor agent[J].Current Pharmarceutical Biotechnology,2006,7(6):441-448.
[24] RIBATTI D,VACCA A.Therapeutic renaissance of thalidomide in the treatment of haematological malignancies[J].Leukemia,2005,19(9):1525-1531.
[25] WU T,YU G Y,XIAO J,et al.Fostering efficacy and toxicity evaluation of traditional Chinese medicine and natural products:Chick embryo as a high throughput model bridging in vitro and in vivo studies[J]. Pharmacological Research,2018,133:21-34.
[26] DUAN Z,DENG J,DONG Y,et al.Anticancer effects of ginsenoside Rk3 on non-small cell lung cancer cells:In vitro and in vivo[J]. Food & Function,2017,8(10):3723-3736.
[27] LOU C,ZHU Z,ZHAO Y,et al.Arctigenin,a lignan from Arctium lappa L.,inhibits metastasis of human breast cancer cells through the downregulation of MMP-2/-9 and heparanase in MDA-MB-231 cells[J].Oncology Reports,2017,37(1):179-184.
[28] GRACE I S,BIRAULT A.Nanoparticles characterization using the CAM assay[J].Enzymes, 2019,46:129-160.
[29] RIBATTI D,ANNESE T,TAMMA R.The use of the chick embryo CAM assay in the study of angiogenic activiy of biomaterials[J].Microvascular Research,2020,131:104026.
[30] RIBATTI D,VACCA A,RANIERI G,et al.The chick embryo chorioallantoic membrane as an in vivo wound healing model[J].Pathology Research and Practice,1996,192:1068-1076.
[31] FDA WOUND HEALING CLINICAL FOCUS GROUP.Guidance for industry:Chronic cutaneous ulcer and burn wounds-developing products for treatment[J].Wound Repair Regen,2001,9(4):258-268.
[32] 王恒,殷慧群,章孝荣.鸡胚模型在生物研究中的应用进展[J].生命科学,2009,21(2):312-315. WANG H,YIN H Q,ZHANG X R.Research advances of chick embryo model in biological experiments[J].Chinese Bulletin of Life Sciences,2009,21(2):312-315.(in Chinese)
[33] 牛子文,常艳凯,王克,等.隐孢子虫体外培养模型研究进展[J].中国寄生虫学与寄生虫病杂志,2020,38(3):395-399. NIU Z W,CHANG Y K,WANG K,et al.Research progresson the in vitro culture model of Cryptosporidium species[J].Chinese Journal of Parasitology and Parasitic Diseases,2020,38(3):395-399.(in Chinese)
[34] RIBATTI D.The use of the chick embryo chorioallantoic membrane as experimental model to study virus growth and to test the clonal selection hypothesis.The contribution of Sir Mac Farlane Burnet[J].Immunology Letters, 2018,200:1-4.
[35] KRAUS B,FIRCKS S,FEIGL S,et al.Avian cell line-technology for large scale vaccine production[J].BMC Proceedings,2011,5(Suppl 8):P52.
[36] OGURA H,FUJIWARA T.Establishment and characterization of a virus-free chick cell line[J].Acta Medica Okayama,1987,41(3):141-143.
[37] SMITH K A,COLVIN C J,WEBER P S D,et al.High titer growth of human and avian influenza viruses in an immortalized chick embryo cell line without the need for exogenous proteases[J].Vaccine,2008,26(29-30):3778-3782.
[38] COUSSENS P M,SMITH K A,WEBER P S,et al.Immortalized chick embryo cell line adapted to serum-free growth conditions and capable of replicating human and reassortant H5N1 influenza strains for vaccine production[J].Vaccine,2011,29(47):8661-8668.
[39] KELLY R B S,JENNA L,CARTER,et al.The PBS-12SF cell line:Development of an alternative cell line for influenza vaccine production[J].Journal of Vaccines and Vaccination,2016,7(6):1-3.
[40] MEHTALI M,CHAMPION P,LEON A.Production of viral vaccines in suspension on avian embryonic derived stem cell lines[P].US-Patent:US 9701945B2,2015.
[41] OLIVIER S,JACOBY M,BRILLON C,et al.EB66 cell line,a duck embryonic stem cell-derived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity[J].mAbs,2010,2:405-415.
[42] BROWN S W,MEHTALI M.The avian EB66(R) cell line,application to vaccines,and therapeutic protein production[J].PDA Journal of Pharmaceutical Science and Technology, 2010,64(5):419-425.
[43] GENZEL Y.Designing cell lines for viral vaccine production:Where do we stand?[J].Biotechnology Journal,2015,10(5):728-740.
[44] VAZQUEZ R D,GENZEL Y,JORDAN I,et al.High-cell-density cultivations to increase MVA virus production[J].Vaccine,2018,36(22):3124-3133.
[45] FU Y,CHEN Z,LI C,et al.Establishment of a duck cell line susceptible to duck hepatitis virus type 1[J].Journal of Virological Methods,2012,184(1-2):41-45.
[46] MONDAL B,RASOOL T J,RAM H,et al.Propagation of vaccine strain of duck enteritis virus in a cell line of duck origin as an alternative production system to propagation in embryonated egg[J].Biologicals,2010,38(3):401-406.
[47] LI Q,LI Y,XIA J,et al.Virulence of Salmonella enterica serovar Pullorum isolates compared using cell-based and chicken embryo infection models[J].Poultry Science,2019,98(3):1488-1493.
[48] REKHA K,SIVASUBRAMANIAN C,CHUNG I M,et al.Growth and replication of infectious bursal disease virus in the DF-1 cell line and chicken embryo fibroblasts[J].Biomed Research International,2014,2014:494835.
[49] RONG S,WHEELER D,WEBER F.Efficient Marek's disease virus (MDV) and herpesvirus of turkey infection of the QM7 cell line that does not contain latent MDV genome[J].Avian Pathology,2014,43(5):414-419.
[50] SCHNITZLEIN W M,TRIPATHY D N.Replication of infectious laryngotracheitis virus in a quail cell line,QT-35[J].Avian Disases, 1995,39(3):528-531.
[51] LU Y,WEST F D,JORDAN B J,et al.Avian-induced pluripotent stem cells derived using human reprogramming factors[J].Stem Cells and Development,2012,21:394-403.
[52] SHITTU I,ZHU Z,LU Y,et al.Development,characterization and optimization of a new suspension chicken-induced pluripotent cell line for the production of Newcastle disease vaccine[J].Biologicals,2016,44:24-32.
[53] BYUN S J,JI M R,JANG Y J,et al.Human extracellular superoxide dismutase (EC-SOD) expression in transgenic chicken[J].BMB Reports,2013,46(8):404-409.
[54] KOO B C,KWON M S,LEE H,et al.Tetracycline-dependent expression of the human erythropoietin gene in transgenic chickens[J].Transgenic Research,2010,19(3):437-447.
[55] PARK T S,LEE H G,MOON J K,et al.Deposition of bioactive human epidermal growth factor in the egg white of transgenic hens using an oviduct-specific minisynthetic promoter[J].FASEB Journal,2015,29(6):2386-2396.
[56] SHERIDAN C.FDA approves ‘farmaceutical’ drug from transgenic chickens[J].Nature Biotechnology,2016,34(2):117-119.
[57] ZHANG L,LUO S,ZHANG B L.Glycan analysis of therapeutic glycoproteins[J].mAbs,2016,8(2):205-215.
[58] HOUDE D,PENG Y,BERKOWITZ S A,et al.Post-translational modifications differentially affect IgG1 conformation and receptor binding[J].Molecular& Cellular Proteomics,2010,9(8):1716-1728.
[59] CHUNG S,QUARMBY V,GAO X,et al.Quantitative evaluation of fucose reducing effects in a humanized antibody on Fcγ receptor binding and antibody-dependent cell-mediated cytotoxicity activities[J].mAbs,2012,4(3):326-340.
[60] KIM Y M,PARK J S,KIM S K,et al.The transgenic chicken derived anti-CD20 monoclonal antibodies exhibits greater anti-cancer therapeutic potential with enhanced Fc effector functions[J].Biomaterials,2018,167:58-68.