
前段时间曾有研究表明,人体细胞可被重新“编程”,回到干细胞的状态,成为被诱导多能干细胞(iPSC)。研究者之一兰扎(Lanza)大胆设想,如果找到血型为O型RhD阴性者提供体细胞,重新编程回到iPSC,再用其iPSC培养出红细胞,那么这样O型RhD阴性的红细胞将可能解决目前输血相关的一系列问题,包括血源紧张、输血传播疾病等。

图1 用胚胎干细胞培育出的红细胞形态(放大1000倍)

图2 正常人红细胞与培育出红细胞的氧解离曲线极其接近

图3a 培养出的原红细胞去核后形态(放大1000倍)3b 人血中红细胞的形态(放大1000倍)
图4 红细胞去核过程
研究者以人胚胎干细胞为“原料”,培育出与人正常红细胞形态和功能接近的成红细胞,经过去核这一关键步骤,成红细胞成功变为没有细胞核的成熟红细胞。
原始出处:
Blood,DOI 10.1182/blood-2008-05-157198,Shi-Jiang Lu, Robert Lanza
Biological properties and enucleation of red blood cells from human embryonic stem cells
Shi-Jiang Lu, Qiang Feng, Jennifer S. Park, Loyda Vida, Bao-Shiang Lee, Michael Strausbauch, Peter J. Wettstein, George R. Honig, and Robert Lanza*
R&D, Advanced Cell Technology, Worcester, MA, United States
Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, United States
Protein Research Laboratory, University of Illinois at Chicago, Chicago, IL, United States
Departments of Surgery and Immunology, Mayo Clinic, Rochester, MN, United States
Human erythropoiesis is a complex multistep process that involves the differentiation of early erythroid progenitors to mature erythrocytes. Here we show that it is feasible to differentiate and mature human embryonic stem cells (hESCs) into functional oxygen-carrying erythrocytes on a large scale (1010 to 1011 cells/six-well plate hESCs). We also show for the first time that the oxygen equilibrium curves of the hESC-derived cells are comparable to normal red blood cells (RBCs) and respond to changes in pH and 2,3-diphosphoglyerate. Although these cells mainly expressed fetal and embryonic globins, they also possessed the capacity to express the adult definitive
-globin chain upon further maturation in vitro. PCR and globin chain specific immunofluorescent analysis showed that the cells increased expression of
-globin (increased from 0% to over 16%) after in vitro culture. Importantly, the cells underwent multiple maturation events, including a progressive decrease in size, increase in glycophorin A expression, and chromatin and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to over 60% of the cells generating RBCs with a diameter of approximately 6-8 µm. The results show that it is feasible to differentiate and mature hESCs into functional oxygen-carrying erythrocytes on a large scale.