利用自控系统全自动培养 IPSC 和分化为 IMSCS

IF 3.7 3区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
L. Herbst , A. Felser , F. Groten , G. Shaw , M. Murphy , B. Nießing , R. Schmitt
{"title":"利用自控系统全自动培养 IPSC 和分化为 IMSCS","authors":"L. Herbst ,&nbsp;A. Felser ,&nbsp;F. Groten ,&nbsp;G. Shaw ,&nbsp;M. Murphy ,&nbsp;B. Nießing ,&nbsp;R. Schmitt","doi":"10.1016/j.jcyt.2024.03.082","DOIUrl":null,"url":null,"abstract":"<div><h3>Background &amp; Aim</h3><p>Although major developments in the field of regenerative medicine have been made, osteoarthritis (OA) remains one of the major illnesses of our day. Mesenchymal stem cells (MSCs) have been suggested as a potential therapy for OA. The clinical success of MSCs has been mixed with several successful phase I and II trials and some phase III trials questioning the efficacy of MSCs as a treatment for OA. These mixed results are partly is attributed to the high degree of biologic variability and lack of standardisation across the manufacturing process of MSCs. MSCs derived from induced pluripotent stem cells (iPSCs) might address some of the heterogeneity derived from donor-to-donor variability. On the manufacturing side, automation is a key technology to increase standardisation and improve iMSC manufacturing in cell quality and manufacturing efficiency.</p></div><div><h3>Methods, Results &amp; Conclusion</h3><p>In the EU project AutoCRAT the systems Autostem and StemCellDiscovery are combined to a fully-automated system for the manufacturing of iPSCs, differentiation to iMSCs and chondrocytes, as well as MSC derived extracellular vesicles (EVs). The Autostem system was previously developed for automated bioreactor-based MSC expansion and subsequent fill-and-finish. For AutoCRAT it was adapted to allow manufacturing of iMSCs and iMSC derived extracellular vesicles (EVs). Similarly, the StemCellDiscovery was developed for plate-based MSC cultivation and microscopic evaluation. This system was adapted to allow for iPSC cultivation and differentiation of iPSCs to iMSCs and chondrocytes.</p><p>This talk reports on the evaluation of this automated solution using a direct comparison of automated versus manual cultivation of iMSCs and iPSCs in terms of efficiency and cell quality. More importantly, it compares manual and automated differentiation of iPSCs to iMSCs. This comparison clearly illustrates the automated system is highly capable in the cultivation of iPSCs and iMSCs. The morphology and fold expansion of iPSCs and iMSCs manufactured in an automated setting is comparable to the manual cultivation. The immunofluorescence and flow cytometry results confirm the automated system is capable of manufacturing high-quality iPSCs and iMSCs. Comparing automated and manual differentiation of iPSCs to iMSCs illustrates the capabilities of the AutoCRAT system in manufacturing of iPSC derived cell therapies. The data presented here highlights the importance of automation for the standardised and transparent manufacturing of cell therapies.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"FULLY-AUTOMATED CULTIVATION OF IPSCS AND DIFFERENTIATION TO IMSCS USING THE AUTOCRAT SYSTEM\",\"authors\":\"L. Herbst ,&nbsp;A. Felser ,&nbsp;F. Groten ,&nbsp;G. Shaw ,&nbsp;M. Murphy ,&nbsp;B. Nießing ,&nbsp;R. Schmitt\",\"doi\":\"10.1016/j.jcyt.2024.03.082\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background &amp; Aim</h3><p>Although major developments in the field of regenerative medicine have been made, osteoarthritis (OA) remains one of the major illnesses of our day. Mesenchymal stem cells (MSCs) have been suggested as a potential therapy for OA. The clinical success of MSCs has been mixed with several successful phase I and II trials and some phase III trials questioning the efficacy of MSCs as a treatment for OA. These mixed results are partly is attributed to the high degree of biologic variability and lack of standardisation across the manufacturing process of MSCs. MSCs derived from induced pluripotent stem cells (iPSCs) might address some of the heterogeneity derived from donor-to-donor variability. On the manufacturing side, automation is a key technology to increase standardisation and improve iMSC manufacturing in cell quality and manufacturing efficiency.</p></div><div><h3>Methods, Results &amp; Conclusion</h3><p>In the EU project AutoCRAT the systems Autostem and StemCellDiscovery are combined to a fully-automated system for the manufacturing of iPSCs, differentiation to iMSCs and chondrocytes, as well as MSC derived extracellular vesicles (EVs). The Autostem system was previously developed for automated bioreactor-based MSC expansion and subsequent fill-and-finish. For AutoCRAT it was adapted to allow manufacturing of iMSCs and iMSC derived extracellular vesicles (EVs). Similarly, the StemCellDiscovery was developed for plate-based MSC cultivation and microscopic evaluation. This system was adapted to allow for iPSC cultivation and differentiation of iPSCs to iMSCs and chondrocytes.</p><p>This talk reports on the evaluation of this automated solution using a direct comparison of automated versus manual cultivation of iMSCs and iPSCs in terms of efficiency and cell quality. More importantly, it compares manual and automated differentiation of iPSCs to iMSCs. This comparison clearly illustrates the automated system is highly capable in the cultivation of iPSCs and iMSCs. The morphology and fold expansion of iPSCs and iMSCs manufactured in an automated setting is comparable to the manual cultivation. The immunofluorescence and flow cytometry results confirm the automated system is capable of manufacturing high-quality iPSCs and iMSCs. Comparing automated and manual differentiation of iPSCs to iMSCs illustrates the capabilities of the AutoCRAT system in manufacturing of iPSC derived cell therapies. The data presented here highlights the importance of automation for the standardised and transparent manufacturing of cell therapies.</p></div>\",\"PeriodicalId\":50597,\"journal\":{\"name\":\"Cytotherapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-05-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cytotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1465324924001701\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotherapy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1465324924001701","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景& 目的虽然再生医学领域取得了重大进展,但骨关节炎(OA)仍是当今的主要疾病之一。间充质干细胞(MSCs)被认为是治疗骨关节炎的一种潜在疗法。间充质干细胞的临床疗效参差不齐,有几项成功的I期和II期试验,也有一些III期试验对间充质干细胞治疗OA的疗效提出质疑。这些喜忧参半的结果部分归因于间充质干细胞的生物可变性较高,以及间充质干细胞的整个制造过程缺乏标准化。从诱导多能干细胞(iPSC)中提取的间充质干细胞可解决因供体间差异而产生的部分异质性问题。在制造方面,自动化是提高标准化、改善 iMSC 制造的细胞质量和制造效率的关键技术。在欧盟项目 AutoCRAT 中,Autostem 系统和 StemCellDiscovery 系统结合成一个全自动系统,用于制造 iPSCs、分化为 iMSCs 和软骨细胞以及间充质干细胞衍生的细胞外囊泡 (EV)。Autostem 系统之前是为基于生物反应器的间充质干细胞自动扩增和后续填充与完成而开发的。在 AutoCRAT 系统中,该系统进行了调整,以便生产 iMSCs 和 iMSC 衍生的细胞外囊泡 (EVs)。同样,StemCellDiscovery 也是为基于平板的间充质干细胞培养和显微镜评估而开发的。本讲座通过直接比较 iMSCs 和 iPSCs 的自动化与人工培养在效率和细胞质量方面的差异,报告了对这一自动化解决方案的评估。更重要的是,它比较了人工和自动化分化 iPSCs 到 iMSCs 的过程。这一比较清楚地表明,自动化系统在培养 iPSCs 和 iMSCs 方面具有很强的能力。自动培养出的 iPSCs 和 iMSCs 在形态和褶皱扩展方面与人工培养相当。免疫荧光和流式细胞术结果证实,自动化系统能够制造出高质量的 iPSCs 和 iMSCs。将 iPSCs 自动分化为 iMSCs 与人工分化进行比较,说明了 AutoCRAT 系统在制造 iPSC 衍生细胞疗法方面的能力。这里展示的数据突出了自动化对于细胞疗法标准化和透明化生产的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
FULLY-AUTOMATED CULTIVATION OF IPSCS AND DIFFERENTIATION TO IMSCS USING THE AUTOCRAT SYSTEM

Background & Aim

Although major developments in the field of regenerative medicine have been made, osteoarthritis (OA) remains one of the major illnesses of our day. Mesenchymal stem cells (MSCs) have been suggested as a potential therapy for OA. The clinical success of MSCs has been mixed with several successful phase I and II trials and some phase III trials questioning the efficacy of MSCs as a treatment for OA. These mixed results are partly is attributed to the high degree of biologic variability and lack of standardisation across the manufacturing process of MSCs. MSCs derived from induced pluripotent stem cells (iPSCs) might address some of the heterogeneity derived from donor-to-donor variability. On the manufacturing side, automation is a key technology to increase standardisation and improve iMSC manufacturing in cell quality and manufacturing efficiency.

Methods, Results & Conclusion

In the EU project AutoCRAT the systems Autostem and StemCellDiscovery are combined to a fully-automated system for the manufacturing of iPSCs, differentiation to iMSCs and chondrocytes, as well as MSC derived extracellular vesicles (EVs). The Autostem system was previously developed for automated bioreactor-based MSC expansion and subsequent fill-and-finish. For AutoCRAT it was adapted to allow manufacturing of iMSCs and iMSC derived extracellular vesicles (EVs). Similarly, the StemCellDiscovery was developed for plate-based MSC cultivation and microscopic evaluation. This system was adapted to allow for iPSC cultivation and differentiation of iPSCs to iMSCs and chondrocytes.

This talk reports on the evaluation of this automated solution using a direct comparison of automated versus manual cultivation of iMSCs and iPSCs in terms of efficiency and cell quality. More importantly, it compares manual and automated differentiation of iPSCs to iMSCs. This comparison clearly illustrates the automated system is highly capable in the cultivation of iPSCs and iMSCs. The morphology and fold expansion of iPSCs and iMSCs manufactured in an automated setting is comparable to the manual cultivation. The immunofluorescence and flow cytometry results confirm the automated system is capable of manufacturing high-quality iPSCs and iMSCs. Comparing automated and manual differentiation of iPSCs to iMSCs illustrates the capabilities of the AutoCRAT system in manufacturing of iPSC derived cell therapies. The data presented here highlights the importance of automation for the standardised and transparent manufacturing of cell therapies.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cytotherapy
Cytotherapy 医学-生物工程与应用微生物
CiteScore
6.30
自引率
4.40%
发文量
683
审稿时长
49 days
期刊介绍: The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信