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Wnt1 Accelerates an Ex Vivo Expansion of Human Cord Blood CD34+CD38− Cells

机译:Wnt1加速人脐带血CD34 + CD38−细胞的体外扩增

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摘要

Cord blood hematopoietic stem cells (CB-HSCs) transplantation has been increasing gradually with facing the limitation of insufficient quantity of HSCs in each CB unit. Therefore, efficient expansion methods which can maintain stem cell characteristics are needed. In this study, umbilical CB-CD34+ cells were cultured in two different cytokine cocktails: 4 factors (4F = Flt3-L, SCF, IL-6, and TPO) and 5 factors (5F = Wnt1 + 4F) in both serum and serum-free media. The data revealed that the best condition to accelerate an expansion of CD34+CD38 cells was serum-free culture condition supplemented with 5F (5F KSR). This condition yielded 24.3 ± 2.1 folds increase of CD34+CD38 cells. The expanded cells exhibited CD34+ CD38 CD133+ CD71low CD33low CD3 CD19 markers, expressed nanog, oct3/4, c-myc, and sox2 genes, and maintained differentiation potential into lymphoid, erythroid and myeloid lineages. The achievement of CD34+CD38 cells expansion may overcome an insufficient quantity of the cells leading to the improvement of the stem cell transplantation. Altogether, our findings highlight the role of Wnt1 and the new culture condition in stimulating hematopoietic stem/progenitor cells expansion which may offer a new therapeutic avenue for cord blood transplantation, regenerative medicine, stem cell bank applications, and other clinical applications in the future.
机译:脐血造血干细胞(CB-HSCs)移植已逐渐增加,面临着每个CB单元中HSC数量不足的局限性。因此,需要能够维持干细胞特性的有效的扩增方法。在这项研究中,脐带CB-CD34 + 细胞在两种不同的细胞因子混合物中培养:4个因子(4F = Flt3-L,SCF,IL-6和TPO)和5个因子(5F = Wnt1) + 4F)在无血清和无血清培养基中。数据显示,促进CD34 + CD38 -细胞扩增的最佳条件是补充5F(5F KSR)的无血清培养条件。该条件使CD34 + CD38 -细胞增加了24.3±2.1倍。扩增的细胞显示出CD34 + CD38 - CD133 + CD71 low CD33 low CD3 - CD19 -标记可表达nanog,oct3 / 4,c-myc和sox2基因,并保持分化潜能,可分为淋巴样,红系和髓系。 CD34 + CD38 -细胞扩增的实现可能克服了细胞数量不足而导致干细胞移植的改善。总之,我们的发现突出了Wnt1和新的培养条件在刺激造血干/祖细胞扩增中的作用,这可能为脐带血移植,再生医学,干细胞库的应用以及将来的其他临床应用提供新的治疗途径。

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