Aldyn Wildey, Stephen Harrington, Lisa Stehno-Bittel, Francis Karanu
{"title":"Reduction of Activin A gives rise to comparable expression of key definitive endoderm and mature beta cell markers.","authors":"Aldyn Wildey, Stephen Harrington, Lisa Stehno-Bittel, Francis Karanu","doi":"10.2217/rme-2023-0187","DOIUrl":null,"url":null,"abstract":"<p><p><b>Aim:</b> Cell therapies for diabetes rely on differentiation of stem cells into insulin-producing cells, which is complex and expensive. Our goal was to evaluate production costs and test ways to reduce it. <b>Methods:</b> Cost of Goods (COGs) analysis for differentiation was completed and the effects of replacement or reduction of the most expensive item was tested using qRT-PCR, immunohistochemistry, flow cytometry along with glucose-stimulated insulin release. <b>Results:</b> Activin A (AA) was responsible for significant cost. Replacement with small molecules failed to form definitive endoderm (DE). Reducing AA by 50% did not negatively affect expression of beta cell markers. <b>Conclusion:</b> Reduction of AA concentration is feasible without adversely affecting DE and islet-like cell differentiation, leading to significant cost savings in manufacturing.</p>","PeriodicalId":21043,"journal":{"name":"Regenerative medicine","volume":" ","pages":"47-63"},"PeriodicalIF":2.4000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regenerative medicine","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.2217/rme-2023-0187","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/19 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0
Abstract
Aim: Cell therapies for diabetes rely on differentiation of stem cells into insulin-producing cells, which is complex and expensive. Our goal was to evaluate production costs and test ways to reduce it. Methods: Cost of Goods (COGs) analysis for differentiation was completed and the effects of replacement or reduction of the most expensive item was tested using qRT-PCR, immunohistochemistry, flow cytometry along with glucose-stimulated insulin release. Results: Activin A (AA) was responsible for significant cost. Replacement with small molecules failed to form definitive endoderm (DE). Reducing AA by 50% did not negatively affect expression of beta cell markers. Conclusion: Reduction of AA concentration is feasible without adversely affecting DE and islet-like cell differentiation, leading to significant cost savings in manufacturing.
目的:治疗糖尿病的细胞疗法依赖于将干细胞分化为胰岛素分泌细胞,这既复杂又昂贵。我们的目标是评估生产成本,并测试降低成本的方法。方法:使用 qRT-PCR、免疫组织化学、流式细胞术和葡萄糖刺激胰岛素释放法测试替代或减少最昂贵项目的效果。结果显示活化素 A(AA)的成本很高。用小分子替代无法形成确定性内胚层(DE)。将 AA 减少 50%不会对β细胞标记物的表达产生负面影响。结论:降低 AA 浓度是可行的,不会对 DE 和类岛细胞分化产生不利影响,从而大大节约了生产成本。
期刊介绍:
Regenerative medicine replaces or regenerates human cells, tissue or organs, to restore or establish normal function*. Since 2006, Regenerative Medicine has been at the forefront of publishing the very best papers and reviews covering the entire regenerative medicine sector. The journal focusses on the entire spectrum of approaches to regenerative medicine, including small molecule drugs, biologics, biomaterials and tissue engineering, and cell and gene therapies – it’s all about regeneration and not a specific platform technology. The journal’s scope encompasses all aspects of the sector ranging from discovery research, through to clinical development, through to commercialization. Regenerative Medicine uniquely supports this important area of biomedical science and healthcare by providing a peer-reviewed journal totally committed to publishing the very best regenerative medicine research, clinical translation and commercialization.
Regenerative Medicine provides a specialist forum to address the important challenges and advances in regenerative medicine, delivering this essential information in concise, clear and attractive article formats – vital to a rapidly growing, multidisciplinary and increasingly time-constrained community.
Despite substantial developments in our knowledge and understanding of regeneration, the field is still in its infancy. However, progress is accelerating. The next few decades will see the discovery and development of transformative therapies for patients, and in some cases, even cures. Regenerative Medicine will continue to provide a critical overview of these advances as they progress, undergo clinical trials, and eventually become mainstream medicine.