Banco de Sangue de Cordão Umbilical e Placentário, Centro de Transplante de Medula óssea, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Cell Transplant. 2012;21(12):2677-88. doi: 10.3727/096368912X636993. Epub 2012 Apr 2.
In adults, hematopoiesis takes places in the bone marrow, where specialized niches containing mesenchymal nonhematopoietic cells (stroma) harbor the hematopoietic stem cell (HSC). These niches are responsible and essential for the maintenance of HSCs. Attempts to expand HSCs fail to keep the general properties of stem cells, which depend on several niche components difficult to reproduce in in vitro culture systems. Here, we describe a methodology for in vivo study of hematopoietic stroma. We use stroma-loaded macroporous microcarriers implanted in the subcutaneous tissue of experimental animals and show that the ectopic stroma implant (ESI) is able to support hematopoiesis. Moreover, lethally irradiated mice can be rescued by ESI preloaded with HSCs, showing that they function as an ectopic bone marrow. ESI is also shown as a good system to study the role of different niche components. As an example, we used stromas lacking connexin 43 (Cx43) and confirm the importance of this molecule in the maintenance of the HSC niche in vivo. We believe ESI can work as an ectopic bone marrow allowing in vivo testing of different niches components and opening new avenues for the treatment of a variety of hematologic conditions particularly when stromal cell defects are the main cause of disease.
在成年人中，造血发生在骨髓中，其中包含间充质非造血细胞（基质）的专门龛位容纳造血干细胞（HSC）。这些龛位负责并对于维持 HSCs 是必不可少的。扩大 HSCs 的尝试无法保持干细胞的一般特性，这取决于几个难以在体外培养系统中复制的龛位成分。在这里，我们描述了一种用于体内研究造血基质的方法。我们使用负载基质的大孔微载体植入实验动物的皮下组织，并表明异位基质植入（ESI）能够支持造血。此外，预先加载 HSCs 的 ESI 可以拯救致死性辐射的小鼠，表明它们充当异位骨髓。ESI 还被证明是研究不同龛位成分作用的良好系统。例如，我们使用缺乏连接蛋白 43（Cx43）的基质，并证实该分子在体内维持 HSC 龛位中的重要性。我们相信 ESI 可以作为异位骨髓，允许在体内测试不同的龛位成分，并为治疗各种血液疾病开辟新途径，特别是当基质细胞缺陷是疾病的主要原因时。
