Red blood cell generation from human induced pluripotent stem cells: perspectives for transfusion medicine
Red blood cell generation from human induced pluripotent stem cells: perspectives for transfusion medicine
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DOI：
10.3324/haematol.2010.023556
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发表时间：
2010-10-01
期刊：
影响因子：
--
通讯作者：
Douay, Luc
中科院分区：
文献类型：
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作者：
Lapillonne, Helene;Kobari, Ladan;Douay, Luc
背景体外从STAR细胞制造红细胞是一种确保足够和安全的血细胞产品供应的潜在手段。人类诱导的多能干细胞的体细胞重编程的进展为产生细胞治疗的特定细胞打开了大门。设计与方法与人胚胎干细胞系(H1)相比，从人胎儿(IMR90)和成人成纤维细胞(FD-136)获得的人诱导多能干细胞系(IMR90)和人成纤维细胞系(FD-136)的红系分化和成熟的特征。我们的方案包括两个步骤：(I)在细胞因子和人血浆的存在下，通过形成必要的条件形成类胚体来分化人诱导的多能干细胞，以获得早期的红系分化；(Ii)在细胞因子的存在下，分化/成熟到培养的红细胞阶段。该方案免除了造血祖细胞必须通过造血祖细胞、在细胞基质上共培养以及使用动物来源的蛋白质等主要限制。结果首次报道了人诱导多能干细胞完全分化为能够成熟的确定的红细胞，直到含有胎儿血红蛋白的功能四聚体的去核红细胞。结论人诱导多能干细胞产生的红细胞为同种异体输血产品的开发奠定了基础。这可以通过储存数量非常有限的红细胞表型组合来实现，从而使大量免疫患者能够安全输血。
BackgroundEx vivo manufacture of red blood cells from stern cells is a potential means to ensure an adequate and safe supply of blood cell products. Advances in somatic cell reprogramming of human induced pluripotent stem cells have opened the door to generating specific cells for cell therapy. Human induced pluripotent stem cells represent a potentially unlimited source of stem cells for erythroid generation for transfusion medicine.Design and MethodsWe characterized the erythroid differentiation and maturation of human induced pluripotent stern cell lines obtained from human fetal (IMR90) and adult fibroblasts (FD-136) compared to those of a human embryonic stem cell line (H1). Our protocol comprises two steps: (i) differentiation of human induced pluripotent stem cells by formation of embryoid bodies with indispensable conditioning in the presence of cytokines and human plasma to obtain early erythroid commitment, and (ii) differentiation/maturation to the stage of cultured red blood cells in the presence of cytokines. The protocol dispenses with major constraints such as an obligatory passage through a hematopoietic progenitor, co-culture on a cellular stroma and use of proteins of animal origin.ResultsWe report for the first time the complete differentiation of human induced pluripotent stem cells into definitive erythrocytes capable of maturation up to enucleated red blood cells containing fetal hemoglobin in a functional tetrameric form.ConclusionsRed blood cells generated from human induced pluripotent stem cells pave the way for future development of allogeneic transfusion products. This could be done by banking a very limited number of red cell phenotype combinations enabling the safe transfusion of a great number of immunized patients.