Recent Developments and Future Challenges of Cultured Meat
LI Dan-Yi1,2, XU Han1,2, ZHAO Xiao-Yu1,2, WU Shan-Shan1,2, YANG Lei1,2, BAI Chun-Ling1,2, LI Guang-Peng1,2,*, SU Guang-Hua1,2,*
1 College of Life Sciences, Inner Mongolia University, Hohhot 010040, China; 2 State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Hohhot 010040, China
Abstract:At present, the demand for meat products has increased because of the rapid growth of the population. The livestock system raises a number of environmental and ethical issues. Therefore, the research of artificial meat will have an important impact on the supply of meat products in the future. Artificial meat includes cultured meat and plant protein meat. Among them, cultured meat is the best alternative to conventional meat. However, large-scale production of cultured meat still faces many challenges due to technical difficulties and high costs. In this review, the development process and current technical challenges of cultured meat are introduced, including the selection of cell types for initial culture, factors and regulatory methods which restrict cell proliferation and differentiation, cell culture environment optimization and muscle tissue formation in vitro. This review provides reference for the industrial production of cultured meat.
[1] 高飞, 蔡军, 杨新春. 2012. 体外定向诱导人工诱导多功能干细胞向心肌细胞分化[J]. 心血管病学进展, 33(02): 179-181. (Gao F, Cai J, Yang X C.2012. Differentiating induced pluripotent stem cells into cardiomyocytes[J]. Advances in Cardiovascular Diseases, 33(02): 179-181.) [2] 黄晨辉, 吴振芳, 雷鸣. 2021. 端粒酶及靶向端粒酶抗衰老和肿瘤药物的研究进展[J]. 中国基础科学, 23(06): 35-45. (Huang C H, Wu Z F, Lei M.2021. Research progress on telomerase and potential anti-aging and tumor drugs targeting telomerase[J]. China Basic Science, 23(06): 35-45.) [3] 凌德凤, 王力仪, 单体中. 2021. 脂肪细胞去分化及其调控机制研究进展[J]. 中国畜牧杂志, 57(08): 21-28. (Ling D F, Wang L Y, Shan T Z.2021. Research progress on adipocytes dedifferentiation and its regulatory mechanism[J]. Chinese Journal of Animal Science, 57(08): 21-28.) [4] 刘芳, 王盼娣, 熊小娟, 等. 2022. 人造肉技术发展现状、安全性评价和监管以及消费者接受度[J]. 中国食物与营养, 28(01): 5-9;56. (Liu F, Wang P D, Xiong X J, et al.2022. Development status of artificial meat technology, safety evaluation and supervision and consumer acceptance[J]. Food and Nutrition in China, 28(01): 5-9;56.) [5] 王崇民. 2022. 欧洲培养鱼肉领先企业Bluu Seafood与中国领先细胞培养肉公司CellX正式达成合作关系[J]. 食品安全导刊, (14): 5. (Wang C M. 2022. Bluu seafood, a leading enterprise of cultured fish in Europe, and cellx, a leading cell culture meat company in China, officially reached a cooperative relationship[J]. China Food Safety Magazine, (14): 5.) [6] 王守伟, 孙宝国, 李石磊, 等. 2021. 生物培育肉发展现状及战略思考[J]. 食品科学, 42(15): 1-9. (Wang S W, Sun B G, L S L, et al.2021. Development status and strategic thinking of cultivated meat[J]. Food Science, 42(15): 1-9.) [7] 辛良杰, 李鹏辉, 范玉枝. 2018. 中国食物消费随人口结构变化分析[J]. 农业工程学报, 34(14): 296-302. (Xin L J, Li P H, Fan Y Z.2018. Change of food consumption with population age structure in China[J]. Transactions of the Chinese Society of Agricultural Engineering, 34(14): 296-302. ) [8] 薛薇. 2021. 植物蛋白肉的研究现状[J]. 食品工程, (04): 33-36. (Xue W. 2021. Research status of plant protein meat[J]. Food Engineering, (04): 33-36. ) [9] 张斌, 屠康. 2020. 传统肉类替代品——人造肉的研究进展[J]. 食品工业科技, 41(09): 327-333. (Zhang B, Tu K.2020. The research advance of traditional meat substitutes-artificial meat[J]. Science and Technology of Food Industry, 41(09): 327-333.) [10] 张国强, 赵鑫锐, 李雪良, 等. 2019. 动物细胞培养技术在人造肉研究中的应用[J]. 生物工程学报, 35(08): 1374-1381. (Zhang G Q, Zhao X R, Li X L, et al.2019. Application of cell culture techniques in cultured meat-a review[J]. Chinese Journal of Biotechnology, 35(08): 1374-1381.) [11] 张涵渝. 2018. 端粒和端粒酶结构与作用的研究进展[J]. 信息记录材料, 19(08): 2-4. (Zhang H Y.2018. Research progress on the structure and function of telomere and telomerase[J]. Information Recording Materials, 19(08): 2-4.) [12] 张江丽. 2007. 胚胎发育中骨骼肌组织的形成及调控[J]. 安徽农业科学,(21): 6447-6448;6566. (Zhang J L.2007. Morphogenesis and regulation of skeletal muscle tissue in embryo development[J]. Journal of Anhui Agricultural Sciences,(21): 6447-6448;6566.) [13] 周光宏, 丁世杰, 徐幸莲. 2020. 培养肉的研究进展与挑战[J]. 中国食品学报, 20(05): 1-11. (Zhou G H, Ding S J, Xu X L.2020. Progress and challenges in cultured meat[J]. Journal of Chinese Institute of Food Science and Technology, 20(05): 1-11.) [14] 周景文, 张国强, 赵鑫锐, 等. 2020. 未来食品的发展: 植物蛋白肉与细胞培养肉[J]. 食品与生物技术学报, 39(10): 1-8. (Zhou J W, Zhang G Q, Zhao X R, et al.2020. Future of food: plant-based and cell cultured meat[J]. Journal of Food Science and Biotechnology, 39(10): 1-8.) [15] 周亚楠, 王淑敏, 马小清, 等. 2021. 植物基人造肉的营养特性与食用安全性[J]. 食品安全质量检测学报, 12(11): 4402-4410. (Zhou Y N, Wang S M, Ma X Q, et al.2021. Nutritional characteristics and edible safety of plant-based artificial meat[J]. Food Safety and Quality Detection Technology, 12(11): 4402-4410.) [16] Allan S J, De Bank P A, Ellis M J.2019. Bioprocess design considerations for cultured meat production with a focus on the expansion bioreactor[J]. Frontiers in Sustainable Food Systems, 3, DOI:10.3389/fsufs.2019.00044. [17] Balasubramanian B, Liu W C, Pushparaj K, et al.2021. The epic of in vitro meat production—A fiction into reality[J]. Foods, 10(6): 1395. [18] Bhat Z F, Bhat H, Kumar S.2020. Cultured meat—A humane meat production system[J]. Principles of Tissue Engineering , 5(73): 1369-1388. [19] Bogliotti Y S, Wu J, Vilarino M, et al.2018. Efficient derivation of stable primed pluripotent embryonic stem cells from bovine blastocysts[J]. Proceedings of the National Academy of Sciences of the USA, 115(9): 2090-2095. [20] Cordelle S, Redl A, Schlich P.2022. Sensory acceptability of new plant protein meat substitutes[J]. Food Quality and Preference, 98: 104508. [21] Datar I, Betti M.2009. Possibilities for an in vitro meat production system[J]. Innovative Food Science and Emerging Technologies, 11(1): 13-22. [22] Edelman P D, McFarland D C, Mironov V A, et al.2005. Commentary: In vitro-cultured meat production[J]. Tissue Engineering, 11(5-6): 659-62. [23] FAO.2006. Livestock's Long Shadow-Environmental Issues and Options[R]. FAO publications, https://www.fao.org/3/a0701e/a0701e00.htm. [24] Gao L, Yang M, Wang X, et al.2019. Mstn knockdown decreases the trans-differentiation from myocytes to adipocytes by reducing Jmjd3 expression via the SMAD2/SMAD3 complex[J]. Bioscience, Biotechnology, and Biochemistry, 83(11): 2090-2096. [25] Gao L, Yang M, Wei Z, et al.2020. MSTN mutant promotes myogenic differentiation by increasing demethylase TET1 expression via the SMAD2/SMAD3 pathway[J]. International Journal of Biological Sciences, 16(8): 1324-1334. [26] Ge L X, Kang J, Dong X C, et al.2020. Myostatin site-directed mutation and simultaneous PPARγ site-directed knockin in bovine genome[J]. Journal of cellular physiology, 236(4). [27] Godfray H C J, Aveyard P, Garnett T, et al.2018. Meat consumption, health, and the environment[J]. Science, 361(6399): eaam5324. [28] Harley C B.2002. Telomerase is not an oncogene[J]. Oncogene, 21(4): 494-502. [29] Hocquette J F, Gondret F, Baéza E, et al.2010. Intramuscular fat content in meat-producing animals: development, genetic and nutritional control, and identification of putative markers[J]. Animal, 4(2): 303-319. [30] Kang D H, Louis F, Liu H, et al.2021. Engineered whole cut meat-like tissue by the assembly of cell fibers using tendon-gel integrated bioprinting[J]. Nature Communications, 12(1): 5059. [31] Lam M T, Sim S, Zhu X Y, et al.2006. The effect of continuous wavy micropatterns on silicone substrates on the alignment of skeletal muscle myoblasts and myotubes[J]. Biomaterials, 27(24): 4340-4347. [32] Luiz A J L, Susan G K, Carla F M M, et al.2021. Cultivated meat: Rrecent technological developments, current market and future challenges[J]. Biotechnology Research and Innovation, 5(1): e2021001. [33] MacQueen L A, Alver C G, Chantre C O, et al.2019. Muscle tissue engineering in fibrous gelatin: Implications for meat analogs[J]. NPJ Science of Food, 3(1), DOI: 10.1038/s41538-019-0054-8. eCollection 2019. [34] Nicole O, Elizabeth S, Diego B, et al.2020. A New Edible film to produce in vitro meat[J]. Foods, 9(2): 185. [35] O'Neill E N, Cosenza A, Baar K, et al.2021. Considerations for the development of cost-effective cell culture media for cultivated meat production[J]. Comprehensive Reviews in Food Science and Food Safety, 20(1): 686-709. [36] Pajčin I, Knežić T, Savic A I, et al.2022. Bioengineering outlook on cultivated meat production[J]. Micromachines (Basel), 13(3): 402. [37] Pandurangan M, Kim D H.2015. A novel approach for in vitro meat production[J]. Applied Microbiology and Biotechnology, 99(13): 5391-5. [38] Post M J.2014. Cultured beef: Medical technology to produce food[J]. Journal of the Science of Food and Agriculture, 94(6): 1039-1041. [39] Reiss J, Robertson S, Suzuki M.2021. Cell sources for cultivated meat: Applications and considerations throughout the production workflow[J]. International Journal of Molecular Sciences, 22(14): 7513. [40] Seah J S H, Singh S, Tan L P, et al.2022. Scaffolds for the manufacture of cultured meat[J]. Critical Reviews in Biotechnology, 42(2): 311-323. [41] Van der Valk J, Brunner D, De Smet K, et al.2010. Optimization of chemically defined cell culture media - Replacing fetal bovine serum in mammalian in vitro methods[J]. Toxicology in Vitro, 24(4): 1053-1063. [42] Yang L, Liu X, Song L, et al.2019. Inhibiting repressive epigenetic modification promotes telomere rejuvenation in somatic cell reprogramming[J]. The FASEB Journal, 33(12): 13982-13997. [43] Zhang G Q, Zhao X R, Li X L, et al.2020. Challenges and possibilities for bio-manufacturing cultured meat[J]. Trends in Food Science & Technology, 97: 443-450. [44] Zheng Y Y, Chen Y, Zhu H Z, et al.2022. Production of cultured meat by culturing porcine smooth muscle cells in vitro with food grade peanut wire-drawing protein scaffold[J]. Food Research International, 159: 111561. [45] Zheng Y Y, Zhu H Z, Wu Z Y, et al.2021. Evaluation of the effect of smooth muscle cells on the quality of cultured meat in a model for cultured meat[J]. Food Research International, 150(Pt A): 110786.