REPROCELL Europe Ltd, Thomson Pavilion, Todd Campus, West of Scotland Science Park, Acre Road, Glasgow, G20 0XA, United Kingdom.
Division of Respiratory Medicine, Department of Medicine, Box 157, Level 5, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge, CB20QQ, United Kingdom.
N Biotechnol. 2021 Jul 25;63:1-9. doi: 10.1016/j.nbt.2021.02.001. Epub 2021 Feb 12.
The promise of using induced pluripotent stem cells (iPSCs) for cellular therapies has been hampered by the lack of easily isolatable and well characterized source cells whose genomes have undergone minimal changes during their processing. Blood-derived late-outgrowth endothelial progenitor cells (EPCs) are used for disease modeling and have potential therapeutic uses including cell transplantation and the translation of induced pluripotent stem cell (iPSC) derivatives. However, the current isolation of EPCs has been inconsistent and requires at least 40-80 mL of blood, limiting their wider use. In addition, previous EPC reprogramming methods precluded the translation of EPC-derived iPSCs to the clinic. Here a series of clinically-compatible advances in the isolation and reprogramming of EPCs is presented, including a reduction of blood sampling volumes to 10 mL and use of highly efficient RNA-based reprogramming methods together with autologous human serum, resulting in clinically relevant iPSCs carrying minimal copy number variations (CNVs) compared to their parent line.
使用诱导多能干细胞（iPSCs）进行细胞治疗的前景受到限制，因为缺乏易于分离和特征明确的源细胞，这些细胞在处理过程中基因组发生的变化很小。血液衍生的晚期成血管内皮祖细胞（EPCs）用于疾病建模，具有潜在的治疗用途，包括细胞移植和诱导多能干细胞（iPSC）衍生物的转化。然而，目前 EPC 的分离方法并不一致，需要至少 40-80 毫升的血液，限制了它们的广泛应用。此外，以前的 EPC 重编程方法排除了 EPC 衍生的 iPSCs 向临床的转化。本文介绍了一系列在 EPC 分离和重编程方面具有临床兼容性的进展，包括将血液采样量减少到 10 毫升，以及使用高效的基于 RNA 的重编程方法和自体人血清，与亲本系相比，产生了具有最小拷贝数变异（CNV）的临床相关 iPSCs。
