Versatile humanized niche model enables study of normal and malignant human hematopoiesis
Versatile humanized niche model enables study of normal and malignant human hematopoiesis
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DOI：
10.1172/jci89364
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发表时间：
2017-02-01
影响因子：
15.9
通讯作者：
Bonnet, Dominique
中科院分区：
文献类型：
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作者：
Abarrategi, Ander;Foster, Katie;Bonnet, Dominique
BM 生态位由特定组织和细胞形成的严格控制的微环境组成，调节造血干细胞 (HSC) 的行为。在这里，我们提供了一个 3D 模型，该模型可在不同的 BM 生态位组件中进行调节，并且在体外和体内均适用于研究正常和恶性造血的维持。使用支架，我们测试了不同基质细胞类型支持人类造血干细胞的能力。事实证明，涂有人间充质基质细胞（hMSC）的支架在植入体内时在 HSC 植入和长期维持方面具有优越性。此外，我们发现hMSC涂层支架可以被调节形成人源化骨组织，这也能够支持人类HSC植入。重要的是，hMSC涂层的人源化支架能够支持白血病患者细胞在体内的生长，包括不会植入免疫缺陷小鼠的BM的样品的生长。这些结果表明 s.c.植入基质细胞的 3D 载体支架中的植入方法是研究人类造血作用的有效体内生态位模型。该模型的各种利基组成部分可以根据具体情况进行更改，以改善非移植急性髓系白血病 (AML) 样本的移植。
The BM niche comprises a tightly controlled microenvironment formed by specific tissue and cells that regulates the behavior of hematopoietic stem cells (HSCs). Here, we have provided a 3D model that is tunable in different BM niche components and useful, both in vitro and in vivo, for studying the maintenance of normal and malignant hematopoiesis. Using scaffolds, we tested the capacity of different stromal cell types to support human HSCs. Scaffolds coated with human mesenchymal stromal cells (hMSCs) proved to be superior in terms of HSC engraftment and long-term maintenance when implanted in vivo. Moreover, we found that hMSC-coated scaffolds can be modulated to form humanized bone tissue, which was also able to support human HSC engraftment. Importantly, hMSC-coated humanized scaffolds were able to support the growth of leukemia patient cells in vivo, including the growth of samples that would not engraft the BM of immunodeficient mice. These results demonstrate that an s.c. implantation approach in a 3D carrier scaffold seeded with stromal cells is an effective in vivo niche model for studying human hematopoiesis. The various niche components of this model can be changed depending on the context to improve the engraftment of nonengrafting acute myeloid leukemia (AML) samples.