细胞培养肉的生物伦理学思考

近年来,为了解决人类社会发展和环境资源的矛盾日益突出的问题,人造肉越来越多的进入人们的视野。通常所说的人造肉,可以分为植物蛋白肉和细胞培养肉。其中植物蛋白肉已经逐步开始商业化,细胞培养肉采用动物细胞进行培养,与真实肉制品更为接近。文中在分析细胞培养肉本质基础上,探讨细胞培养肉对肉类生产行业、消费者群体以及人类未来可持续发展的积极意义。在生物伦理学的视角下,研发和生产细胞培养肉有助于保障人类社会的可持续发展、提升动物福利、减少资源需求、改善肉制品营养功能,并为其他行业的发展提供新的增长点。此外,对于细胞培养肉生产涉及的食品安全、技术滥用、技术监管层面上的伦理风险提出进行了深入思考,希望能从生物伦理学的层面为人造肉行业的可持续发展提供参考。     

动物细胞大规模培养技术

近年来,动物细胞大规模培养技术在生物技术领域成为最受关注的热点之一,并开始广泛应用于生物医药的研发和生产过程中。以生物反应器技术为基础的动物细胞大规模培养技术平台,正逐步被建立起来并日益走向成熟,成为推动生物医药产业快速发展的有力工具。结合该技术目前的应用水平和最新进展,分析了不同细胞培养工艺之间的内在差异,以探索这一技术的未来发展方向。     

用于重组抗体生产的细胞大规模培养技术

近年来,用于单抗药物生产的动物细胞大规模培养技术发展迅速.此领域的技术进展集中在个性化培养基开发,工艺条件优化等方面.本文总结了用于提高重组抗体表达水平的常用方法,以及细胞培养工艺对抗体药物“关键质量属性”(聚体、降解、糖基化修饰、电荷变异等)的诸多影响.此外,细胞培养工艺在产业化过程面临着工艺放大与技术转移,定性研究与工艺验证等实际问题.未来大规模细胞培养工艺的开发,将进一步借助动物细胞的组学研究成果和新兴的“过程分析技术”.     

大规模动物细胞培养的问题及对策

大规模动物细胞培养在生物技术产业化进程中显示出强大的潜力。本文综述了大规模动物细胞培养过程中出现的问题及其解决办法 ,包括细胞培养环境、基因工程途径改建细胞系及过程监控等。对于这些进展的充分了解对优化细胞培养工艺、提高产品质量具有重要意义     

大规模动物细胞培养的问题及对策

大规模动物细胞培养在生物技术产业化进程中显示出强大的潜力。本文综述了大规模动物细胞培养过程中出现的问题及其解决办法,包括细胞培养环境、基因工程途径改建细胞系及过程监控等。对于这些进展的充分了解对优化细胞培养工艺、提高产品质量具有重要意义     

一种细胞培养发酵罐的评价

人和动物细胞的体外培养在生物学和医学研究中起着重要作用。然而,将动物细胞培养应用于生产却因在获得足够的产额及生物活性方面的困难而受到限制。传统上一直把细胞培养产物用作人类和牲畜的病毒疫苗,这些疫苗至今已大规模应用。在过去的七年中,大规模细胞培养技术已用于α—和β—干扰素的生产。最近,动物细胞培养技术也已用来生产大量的单克隆抗体和一些遗传工程蛋白质。     

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

目的：2019年以来，人造肉技术受到了社会的广泛关注，各种人造肉制品抢占餐饮市场标志着这项技术可能迎来一个转折点，逐步进入大规模商业化阶段。方法：综述了植物蛋白肉和细胞培养肉两种类型的人造肉在技术层面的发展现状，探讨了人造肉的食用安全性和生物安全性以及监管框架，展望了人造肉的市场和消费者接受度。结果：人造肉是肉类生产领域中的一种新模式和新方向，将减少食品工业对传统农业的依赖性，有助于缓解人类日益增长的营养需求和逐渐恶化的生态环境之间的矛盾。结论：本综述将有助于促进人造肉科学研究的进一步发展，并促进其产品市场在有安全保障的基础上稳步发展。     

搅拌式动物细胞反应器研究应用与发展

随着动物细胞表达的治疗型重组蛋白的应用越来越广,动物细胞大规模培养技术备受关注,其中,机械搅拌式动物细胞生物反应器得到了广泛应用。本文对搅拌式动物细胞培养罐的结构功能进行了系统性的介绍,总结了其特性及国内外的研究现状与应用,最后指出其研发尚存在的问题及对未来的展望。     

植物细胞和器官大规模培养研究的进展

植物细胞,组织培养技术的发展,使得许多在实验室进行的研究已向工厂化生产过渡,除了植物细胞培养技术以外,近年来植物器官（茎,芽,根,胚和毛状根等）培养也得到迅速发展,建立了许多培养体系并在各种反应器中进行了探索性的培养实验,尤其毛状根培养越来越受到人们的瞩目,大规模培养技术的日趋完善,为植物生物技术的产业化发展带来巨大的动力。     

植物细胞大规模培养技术产业化浅谈

植物细胞培养技术诞生于20世纪初,随着研究的不断进步,逐步发展出植物组织培养、植物器官培养、原生质体培养、细胞培养、冠瘿瘤培养以及不定根或毛状根培养等技术.20世纪80年代前后,利用植物细胞培养生产植物次生代谢产物的研究成为热点.比如1977年Noguchi等就利用20吨发酵罐进行了烟草细胞培养生产尼古丁实验.1977年Alfernmann等利用毛地黄培养细胞把甲基洋地黄毒苷转化为甲基地戈辛,证明植物细胞的生物转化能力.1985年日本的三井石油化学公司利用紫草细胞大规模培养生产紫草宁,并且投放市场,首次将植物细胞培养技术实现了产业化.     

Techno-economic modeling and assessment of cultivated meat: Impact of production bioreactor scale

Increases in global meat demands cannot be sustainably met with current methods of livestock farming, which has a substantial impact on greenhouse gas emissions, land use, water consumption, and farm animal welfare. Cultivated meat is a rapidly advancing technology that produces meat products by proliferating and differentiating animal stem cells in large bioreactors, avoiding conventional live-animal farming. While many companies are working in this area, there is a lack of existing infrastructure and experience at commercial scale, resulting in many technical bottlenecks such as scale-up of cell culture and media availability and costs. In this study, we evaluate theoretical cultivated beef production facilities with the goal of envisioning an industry with multiple facilities to produce in total 100,000,000 kg of cultured beef per year or ~0.14% of the annual global beef production. Using the computer-aided process design software, SuperPro Designer®, facilities are modeled to create a comprehensive analysis to highlight improvements that can lower the cost of such a production system and allow cultivated meat products to be competitive. Three facility scenarios are presented with different sized production reactors; ~42,000 L stirred tank bioreactor (STR) with a base case cost of goods sold (COGS) of $35/kg, ~211,000 L STR with a COGS of $25/kg, and ~262,000 L airlift reactor (ALR) with a COGS of $17/kg. This study outlines how advances in scaled up bioreactors, alternative bioreactor designs, and decreased media costs are necessary for commercialization of cultured meat products.     

Scientific and Islamic perspectives in relation to the Halal status of cultured meat

Cultured meat is meat produced from stem cell biopsies of cattle. Stem cells were cultured in a bioreactor in the presence of serum to grow the flesh to maturity. Cultured meat technology originated from regenerative medical technology; however, it has been given a new lease of life to produce cultured meat as an innovative food source in the future without involving cattle breeding. This technology can reduce the negative environmental impacts of global warming, water use, soil, and unethical handling of animals. In the excitement of accepting this new technology, the halal status of cultured meat is in question, as it can be produced from embryonic stem cells and myosatellite cells, each of which can be disputed for their halal status. Additionally, the process of culturing and maturation of stem cells involves the use of an impure medium derived from animal blood. Thus, cultured meat is acceptable to Muslims only if the stem cells, medium and scaffold biomaterials used to manufacture it are from Halal sources and shall be in line with the six principles discussed in this study. The discussion is based on Halal and haram animals; Animal slaughtering; Not derived from a source of najs (impurity); Istihalah tammah (perfect substance change); Maslahah (public interest or benefit) and mafsadah (damage); and Darurat (exigency) of cultured meat)).     

Cultivated meat manufacturing: Technology,trends, and challenges

The growing world population, public awareness of animal welfare, environmental impacts and changes in meat consumption leads to the search for novel approaches to food production. Novel foods include products with a new or specifically modified molecular structure, foods made from microorganisms, fungi, algae or insects, as well as from animal cell or tissue cultures. The latter approach is known by various names: “clean meat”, “in vitro meat” and “cell-cultured” or “(cell-)cultivated meat”. Here, cells isolated from agronomically important species are expanded ex vivo to produce cell biomass used in unstructured meat or to grow and differentiate cells on scaffolds to produce structured meat analogues. Despite the fast-growing field and high financial interest from investors and governments, cultivated meat production still faces challenges ranging from cell source choice, affordable expansion, use of cruelty-free and food-grade media, regulatory issues and consumer acceptance. This overview discusses the above challenges and possible solutions and strategies in the production of cultivated meat. The review integrates multifaceted historical, social, and technological insights of the field, and provides both an engaging comprehensive introduction for general interested and a robust perspective for experts.     

Review: Analysis of the process and drivers for cellular meat production

Cell-based meat, also called ‘clean’, lab, synthetic or in vitro meat, has attracted much media interest recently. Consumer demand for cellular meat production derives principally from concerns over environment and animal welfare, while secondary considerations include consumer and public health aspects of animal production, and food security. The present limitations to cellular meat production include the identification of immortal cell lines, availability of cost-effective, bovine-serum-free growth medium for cell proliferation and maturation, scaffold materials for cell growth, scaling up to an industrial level, regulatory and labelling issues and at what stage mixing of myo-, adipo- and even fibrocytes can potentially occur. Consumer perceptions that cell-based meat production will result in improvements to animal welfare and the environment have been challenged, with the outcome needing to wait until the processes used in cell-based meat are close to a commercial reality. Challenges for cell-based meat products include the simulation of nutritional attributes, texture, flavour and mouthfeel of animal-derived meat products. There is some question over whether consumers will accept the technology, but likely there will be acceptance of cell-based meat products, in particular market segments. Currently, the cost of growth media, industry scale-up of specific components of the cell culture process, intellectual property sharing issues and regulatory hurdles mean that it will likely require an extended period for cellular meat to be consistently available in high-end restaurants and even longer to be available for the mass market. The progress in plant-based meat analogues is already well achieved, with products such as the Impossible^TM Burger and other products already available. These developments may make the development of cellular meat products obsolete. But the challenges remain of mimicking not only the nutritional attributes, flavour, shape and structure of real meat, but also the changes in regulation and labelling.     

蛋白质组学技术在肉类鉴别及肉质分析中的应用进展

肉制品是人体中蛋白质和多种微量元素的重要来源,但对于肉制品中肉类的鉴别及品质分析的研究受到了传统方法的限制。近年来,蛋白质组学技术的应用极大地推动了肉类鉴别技术的发展,并对肉质形成的潜在分子机制的研究有着深远的影响。主要介绍了蛋白质组学的概念及其研究策略,全面综述了蛋白质组学技术在肉类鉴别和肉质分析中的应用进展,并展望了其研究前景,以期为肉制品的质量控制及肉质影响因素的研究提供理论依据。     

Animal board invited review: Animal agriculture and alternative meats – learning from past science communication failures

Sustainability discussions bring in multiple competing goals, and the outcomes are often conflicting depending upon which goal is being given credence. The role of livestock in supporting human well-being is especially contentious in discourses around sustainable diets. There is considerable variation in which environmental metrics are measured when describing sustainable diets, although some estimate of the greenhouse gas (GHG) emissions of different diets based on varying assumptions is commonplace. A market for animal-free and manufactured food items to substitute for animal source food (ASF) has emerged, driven by the high GHG emissions of ASF. Ingredients sourced from plants, and animal cells grown in culture are two approaches employed to produce alternative meats. These can be complemented with ingredients produced using synthetic biology. Alternative meat companies promise to reduce GHG, the land and water used for food production, and reduce or eliminate animal agriculture. Some CEOs have even claimed alternative meats will ‘end world hunger’. Rarely do such self-proclamations emanate from scientists, but rather from companies in their efforts to attract venture capital investment and market share. Such declarations are reminiscent of the early days of the biotechnology industry. At that time, special interest groups employed fear-based tactics to effectively turn public opinion against the use of genetic engineering to introduce sustainability traits, like disease resistance and nutrient fortification, into global genetic improvement programs. These same groups have recently turned their sights on the ‘unnaturalness’ and use of synthetic biology in the production of meat alternatives, leaving agriculturists in a quandary. Much of the rationale behind alternative meats invokes a simplistic narrative, with a primary focus on GHG emissions, ignoring the nutritional attributes and dietary importance of ASF, and livelihoods that are supported by grazing ruminant production systems. Diets with low GHG emissions are often described as sustainable, even though the nutritional, social and economic pillars of sustainability are not considered. Nutritionists, geneticists, and veterinarians have been extremely successful at developing new technologies to reduce the environmental footprint of ASF. Further technological developments are going to be requisite to continuously improve the efficiency of animal source, plant source, and cultured meat production. Perhaps there is an opportunity to collectively communicate how innovations are enabling both alternative- and conventional-meat producers to more sustainably meet future demand. This could counteract the possibility that special interest groups who promulgate misinformation, fear and uncertainty, will hinder the adoption of technological innovations to the ultimate detriment of global food security.     

表达外源rhBMP2的CHO细胞株稳定性分析

骨形态发生蛋白2(BMP2)属于TGF-β超家族,是诱导成骨活性最强的BMPs之一, 具有广泛的临床应用的前景。本实验室已成功构建高效表达rhBMP2的重组CHO细胞株, 现选取其中一株表达量最高的细胞rCHO(hBMP2)-C8进行长期体外培养, 并在培养过程中比较了添加和去除压力筛选中使用的MTX对细胞生长, rhBMP2基因拷贝数及rhBMP2分泌蛋白表达的影响;检测了该细胞株在无血清培养基中可以连续表达rhBMP2的时间以及培养基中rhBMP2的温度敏感性等等。该研究为进一步采用动物细胞规模化培养技术生产rhBMP2奠定了基础。     

未来食品的低碳生物制造

受到人口增长过快、社会经济发展水平不平衡、人口老龄化和不健康饮食方式等影响,人类面临着食品和营养缺乏、部分人群中营养相关疾病高发等问题。同时,社会低碳发展的需求呼唤一种可持续的食物供给模式。因此,既能满足消费者口感和营养需求,又是绿色可持续食物供给模式的技术,例如功能糖、人造肉等未来食品技术,受到了广泛的关注。近年,新兴的生物制造技术及产品得到了迅猛发展,将会支撑形成绿色、低碳的未来食品产业,引发传统生产模式的深刻变革,是新兴生物经济的重大战略发展方向。本文聚焦于未来食品——功能糖、微生物蛋白及人造肉等关键辅配料的生物制造技术研究,追踪其在细胞工厂构建、工业环境下菌种测试与过程优化和衍生产品开发等研究的最新进展,展望未来的发展趋势,旨在为微生物制造未来食品的产业发展提供指导。