骨髓移植是一种有效的细胞治疗方式，但受体需要接受骨髓细胞清除(myeloablation)，从而增加了感染风险和死亡率。最近谱系示踪(lineage tracing)研究证明器官中定居型巨噬细胞的自我维持无需血液祖细胞。这一发现促使我们考虑器官靶向的、细胞特异性疗法。在这里，我们使用粒细胞—巨噬细胞集落刺激因子(GM-CSF)受体beta缺陷型(Csf2rb−/−)小鼠制备了一种骨髓细胞失调的动物模型，该模型与人类儿童CSF2RA或CSF2RB缺陷的遗传性肺泡蛋白质沉积症(hereditary pulmonary alveolar proteinosis, hPAP)相同。我们的结果显示：无需骨髓细胞清除，用野生型或Csf2rb基因修正的巨噬细胞进行肺巨噬细胞移植(PMT)，PMT对动物安全，且动物能很好耐受，而且一次移植可修复动物肺部疾病和继发性系统性表现，并使疾病相关生物标志物恢复正常，阻止疾病特异性死亡的出现。PMT的肺泡巨噬细胞和疗效持续至少达一年之久。我们的结果确定了在健康和患病状况下肺泡巨噬细胞数量规模的调节机制，表明肺泡巨噬细胞表型的决定需要GM-CSF，并支持PMT作为儿童hPAP疾病首选的特异性治疗手段。

链接：http://www.nature.com/nature/journal/v514/n7523/full/nature13807.html

文题：Pulmonary macrophage transplantation therapy

摘要：Bone-marrow transplantation is an effective cell therapy but requires myeloablation, which increases infection risk and mortality. Recent lineage-tracing studies documenting that resident macrophage populations self-maintain independently of haematological progenitors prompted us to consider organ-targeted, cell-specific therapy. Here, using granulocyte–macrophage colony-stimulating factor (GM-CSF) receptor-β-deficient (Csf2rb−/−) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA or CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe and well-tolerated and that one administration corrected the lung disease, secondary systemic manifestations and normalized disease-related biomarkers, and prevented disease-specific mortality. PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects. Our findings identify mechanisms regulating alveolar macrophage population size in health and disease, indicate that GM-CSF is required for phenotypic determination of alveolar macrophages, and support translation of PMT as the first specific therapy for children with hPAP.

上文由群晓科苑翻译整理，科学推广，服务民众。他人或机构如需使用，请提供该原始链接地址。

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