Generali M, Kehl D, Meier D, Zorndt D, Atrott K, Saito H, Emmert M Y, Hoerstrup S P
Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland.
Center for Surgical Research, University of Zurich, University Hospital Zurich, Zurich, Switzerland.
Stem Cell Res Ther. 2025 Apr 18;16(1):189. doi: 10.1186/s13287-025-04319-0.
Over the past decade, the field of cell therapy has rapidly expanded with the aim to replace and repair damaged cells and/or tissue. Depending on the disease many different cell types can be used as part of such a therapy. Here we focused on the potential treatment of myocardial infarction, where currently available treatment options are not able to regenerate the loss of healthy heart tissue.
We generated good manufacturing practice (GMP)-compatible cardiomyocytes (iCMs) from transgene- and xenofree induced pluripotent stem cells (iPSCs) that can be seamless adapted for clinical applications. Further protocols were established for replating and freezing/thawing iCMs under xenofree conditions.
iCMs showed a cardiac phenotype, with the expression of specific cardiac markers and absence of pluripotency markers at RNA and protein level. To ensure a pure iCMs population for in vivo applications, we minimized risks of iPSC contamination using RNA-switch technology to ensure safety.
We describe the generation and further processing of xeno- and transgene-free iCMs. The use of GMP-compliant differentiation protocols ab initio facilitates the clinical translation of this project in later stages.
在过去十年中，细胞治疗领域迅速发展，旨在替换和修复受损细胞及/或组织。根据疾病的不同，许多不同类型的细胞可用于此类治疗。在此，我们聚焦于心肌梗死的潜在治疗，目前现有的治疗方案无法使受损的健康心脏组织再生。
我们从无转基因和无外源成分的诱导多能干细胞（iPSC）中生成了符合药品生产质量管理规范（GMP）的心肌细胞（iCM），这些细胞可无缝应用于临床。还建立了在无外源成分条件下对iCM进行传代培养和冻融的进一步方案。
iCM呈现出心脏表型，在RNA和蛋白质水平上表达特定的心脏标志物且无多能性标志物。为确保用于体内应用的iCM群体纯净，我们使用RNA开关技术将iPSC污染风险降至最低以确保安全。
我们描述了无外源成分和无转基因iCM的生成及进一步处理方法。从一开始就使用符合GMP的分化方案有助于该项目在后期阶段向临床转化。
Zotero 插件
