Department of Cell Biology, Albert Einstein College of Medicine Bronx, New York, 10461.
Department of Cell Biology, Albert Einstein College of Medicine Bronx, New York.
Haematologica. 2024 Nov 1;109(11):3705-3720. doi: 10.3324/haematol.2023.284427.
Cultured reticulocytes can supplement transfusion needs and offer promise for drug delivery and immune tolerization. They can be produced from induced pluripotent stem cells (iPSC), but the 45-day culture time and cytokine costs make largescale production prohibitive. To overcome these limitations, we have generated iPSC that express constitutive stem cell factor (SCF) receptor and jak2 adaptor alleles. We show that iPSC lines carrying these alleles can differentiate into self-renewing erythroblasts that can proliferate for up to 70 cell-doubling in a cost-effective, chemically-defined, albumin- and cytokine-free medium. These kitjak2 self-renewing erythroblasts retain the ability to enucleate at a high rate up to senescence. Kitjak2-derived cultured reticulocytes should be safe for transfusion because they can be irradiated to eliminate residual nucleated cells. The kitjak2 cells express blood group 0 and test negative for RhD and other clinically significant red blood cell antigens and have sufficient proliferation capacity to meet global red blood cell needs.
培养的网织红细胞可以补充输血需求，并为药物输送和免疫耐受提供前景。它们可以从诱导多能干细胞（iPSC）中产生，但 45 天的培养时间和细胞因子成本使得大规模生产变得困难。为了克服这些限制，我们已经生成了表达组成型干细胞因子（SCF）受体和 jak2 衔接子等位基因的 iPSC。我们表明，携带这些等位基因的 iPSC 系可以分化为自我更新的红细胞，这些红细胞可以在具有成本效益的、化学定义的、无白蛋白和细胞因子的培养基中增殖多达 70 个细胞倍增。这些 kitjak2 自我更新的红细胞在衰老之前仍能以高比例去核。Kitjak2 衍生的培养的网织红细胞因为可以被辐照以消除残留的有核细胞，所以应该是安全的输血细胞。Kitjak2 细胞表达血型 0，并且对 RhD 和其他临床上有意义的红细胞抗原呈阴性反应，并且具有足够的增殖能力来满足全球对红细胞的需求。
