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首页> 外文期刊>BioResearch open access. >Sustained Engraftment of Cryopreserved Human Bone Marrow CD34+ Cells in Young Adult NSG Mice
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Sustained Engraftment of Cryopreserved Human Bone Marrow CD34+ Cells in Young Adult NSG Mice

机译：低温保存的年轻成年NSG小鼠的冷冻保存的人骨髓CD34 +细胞的植入

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摘要

Hematopoietic stem cells (HSCs) are defined by their ability to repopulate the bone marrow of myeloablative conditioned and/or (lethally) irradiated recipients. To study the repopulating potential of human HSCs, murine models have been developed that rely on the use of immunodeficient mice that allow engraftment of human cells. The NSG xenograft model has emerged as the current standard for this purpose allowing for engraftment and study of human T cells. Here, we describe adaptations to the original NSG xenograft model that can be readily implemented. These adaptations encompass use of adult mice instead of newborns and a short ex vivo culture. This protocol results in robust and reproducible high levels of lympho-myeloid engraftment. Immunization of recipient mice with relevant antigen resulted in specific antibody formation, showing that both T cells and B cells were functional. In addition, bone marrow cells from primary recipients exhibited repopulating ability following transplantation into secondary recipients. Similar results were obtained with cryopreserved human bone marrow samples, thus circumventing the need for fresh cells and allowing the use of patient derived bio-bank samples. Our findings have implications for use of this model in fundamental stem cell research, immunological studies in vivo and preclinical evaluations for HSC transplantation, expansion, and genetic modification.
机译：造血干细胞（HSC）由它们重新增殖骨髓清液化条件和/或（经致命）照射的受体的骨髓的能力来定义。为了研究人类HSC的繁殖潜力，已经建立了小鼠模型，该模型依赖于免疫缺陷小鼠的使用，该小鼠可以植入人类细胞。 NSG异种移植模型已成为目前用于该目的的标准，可用于人类T细胞的移植和研究。在这里，我们描述了对原始NSG异种移植模型的改编，该改编可以很容易地实现。这些改编包括使用成年小鼠代替新生儿和简短的离体培养。该协议可导致强大且可重现的高水平淋巴-骨髓植入。用相关抗原免疫受体小鼠导致特异性抗体形成，表明T细胞和B细胞均具有功能。另外，来自原代受体的骨髓细胞在移植到次要受体后显示出重新繁殖的能力。用冷冻保存的人骨髓样品获得了相似的结果，从而避免了对新鲜细胞的需求，并允许使用患者来源的生物库样品。我们的发现对在基本干细胞研究，体内免疫学研究以及HSC移植，扩增和基因修饰的临床前评估中使用该模型具有重要意义。

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