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首页> 外文期刊>Cell cycle >Rapid lymphocyte reconstitution of unconditioned immunodeficient mice with non-self-renewing multipotent hematopoietic progenitors.
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Rapid lymphocyte reconstitution of unconditioned immunodeficient mice with non-self-renewing multipotent hematopoietic progenitors.

机译：具有非自我更新的多能造血祖细胞的无条件免疫缺陷小鼠的快速淋巴细胞重建。

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摘要

The replacement of abnormal hematopoietic stem cells (HSCs) with normal transplanted HSCs can correct a wide range of hematologic disorders. Here, we provide evidence that transplantation of more differentiated progenitor cells can be used to more rapidly correct lymphoid deficiencies in unconditioned immunocompromised mice. Transplantation of flk2+ multipotent progenitors led to robust B and T cell reconstitution that was maintained for at least 16 weeks. Antigenic challenge at 16 weeks post-transplantation revealed that reconstituted lymphocytes maintained a functional repertoire. In contrast to the persistent lymphocytic engraftment, myeloid chimerism was lost by 12 weeks post-transplantation consistent with the fact that flk2+ progenitors are non-self-renewing. Thus, while more differentiated progenitors are capable of rescuing lymphoid deficiencies, transplantation of HSCs must be used for the correction of non-lymphoid disorders, and, we propose, very long-term immune reconstitution. Based on recent evidence, we discuss novel strategies to achieve the replacement of abnormal HSCs without the use of cytotoxic conditioning regimens.
机译：用正常移植的HSC替代异常的造血干细胞（HSC）可纠正多种血液学疾病。在这里，我们提供了证据，可以将分化程度更高的祖细胞移植用于更快速地纠正无条件免疫受损小鼠的淋巴样缺陷。 flk2 +多能祖细胞的移植导致强大的B和T细胞重构，这种重构可以维持至少16周。移植后16周的抗原攻击显示重组淋巴细胞维持功能库。与持续的淋巴细胞植入相反，移植后12周，骨髓嵌合体丧失了，这与flk2 +祖细胞是非自我更新的事实相一致的。因此，尽管分化程度更高的祖细胞能够挽救淋巴样缺陷，但是必须使用HSC的移植来纠正非淋巴样疾病，并且我们建议长期免疫重建。基于最新证据，我们讨论了无需使用细胞毒性条件疗法即可替代异常HSC的新策略。

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