INSERM, UMR_S938, Proliferation and Differentiation of Stem Cells, Paris, France.
Curr Opin Hematol. 2011 Jul;18(4):249-53. doi: 10.1097/MOH.0b013e3283476129.
In the context of chronic blood supply difficulties, generating cultured red blood cells (cRBCs) in vitro after amplification of stem cells makes sense. This review will focus on the recent findings about the generation of erythroid cells from induced pluripotent stem (iPS) cells and deals with the hurdles and next developments that will occur.
The most proliferative source of stem cells for generating cRBCs is the cord blood, but this source is limited in terms of hematopoietic stem cells and dependent on donations. Pluripotent stem cells are thus the best candidates and potential sources of cRBCs. Critical advances have led towards the in-vitro production of functional RBCs from iPS cells in the last few years.
Because iPS cells can proliferate indefinitely and can be selected for a phenotype of interest, they are potential candidates to organize complementary sources of RBCs for transfusion. Proof of concept of generating cRBCs from iPS cells has been performed, but the procedures need to be optimized to lead to clinical application in blood transfusion. Several crucial points remain to be resolved. Notably these include the choice of the initial cell type to generate iPS cells, the method of reprogramming, that is, to ensure the safety of iPS cells as clinical grade, the optimization of erythrocyte differentiation, and the definition of good manufacturing practice (GMP) conditions for industrial production.
在慢性血液供应困难的情况下,在干细胞扩增后体外生成培养的红细胞(cRBC)是有意义的。本文将重点介绍诱导多能干细胞(iPS)细胞生成红细胞的最新发现,并探讨即将出现的障碍和下一步的发展。
用于生成 cRBC 的最具增殖性的干细胞来源是脐带血,但这种来源在造血干细胞方面有限制,且依赖于捐赠。因此,多能干细胞是生成 cRBC 的最佳候选者和潜在来源。在过去几年中,iPS 细胞在体外生成功能性 RBC 方面取得了重大进展。
由于 iPS 细胞可以无限增殖,并且可以针对感兴趣的表型进行选择,因此它们是组织补充 RBC 用于输血的潜在候选者。已经证明可以从 iPS 细胞生成 cRBC,但需要优化这些程序以实现输血的临床应用。仍有几个关键问题需要解决。值得注意的是,这些问题包括选择生成 iPS 细胞的初始细胞类型、重编程的方法,即确保 iPS 细胞作为临床级别的安全性、红细胞分化的优化以及工业生产的良好生产规范(GMP)条件的定义。