Division of Newbork Medicine, Department of Pediatrics, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
Am J Physiol Lung Cell Mol Physiol. 2012 May 1;302(9):L829-37. doi: 10.1152/ajplung.00347.2011. Epub 2012 Feb 10.
Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity resulting in significant morbidity and mortality. The pathology of BPD is multifactorial and leads to alveolar simplification and distal lung injury. Previous studies have shown a beneficial effect of systemic treatment with bone marrow-derived mesenchymal stromal cells (MSCs) and MSC-conditioned media (MSC-CM) leading to amelioration of the lung parenchymal and vascular injury in vivo in the hyperoxia murine model of BPD. It is possible that the beneficial response from the MSCs is at least in part due to activation of endogenous lung epithelial stem cells. Bronchioalveolar stem cells (BASCs) are an adult lung stem cell population capable of self-renewal and differentiation in culture, and BASCs proliferate in response to bronchiolar and alveolar lung injury in vivo. Systemic treatment of neonatal hyperoxia-exposed mice with MSCs or MSC-CM led to a significant increase in BASCs compared with untreated controls. Treatment of BASCs with MSC-CM in culture showed an increase in growth efficiency, indicating a direct effect of MSCs on BASCs. Lineage tracing data in bleomycin-treated adult mice showed that Clara cell secretory protein-expressing cells including BASCs are capable of contributing to alveolar repair after lung injury. MSCs and MSC-derived factors may stimulate BASCs to play a role in the repair of alveolar lung injury found in BPD and in the restoration of distal lung cell epithelia. This work highlights the potential important role of endogenous lung stem cells in the repair of chronic lung diseases.
支气管肺发育不良（BPD）仍然是早产儿的主要并发症，导致发病率和死亡率显著增加。BPD 的病理学是多因素的，导致肺泡简化和远端肺损伤。先前的研究表明，骨髓间充质基质细胞（MSCs）和 MSC 条件培养基（MSC-CM）的全身治疗具有有益作用，可改善 BPD 高氧血症小鼠模型中的肺实质和血管损伤。MSCs 的有益反应至少部分可能是由于激活内源性肺上皮干细胞。细支气管肺泡干细胞（BASCs）是一种成体肺干细胞群，能够在培养中自我更新和分化，BASCs 在体内对细支气管和肺泡肺损伤有增殖反应。用 MSCs 或 MSC-CM 对新生高氧暴露的小鼠进行全身治疗，与未治疗的对照组相比，BASCs 的数量明显增加。MSC-CM 对 BASCs 的培养显示生长效率增加，表明 MSCs 对 BASCs 有直接作用。博来霉素处理的成年小鼠的谱系追踪数据表明，包括 BASCs 在内的 Clara 细胞分泌蛋白表达细胞能够在肺损伤后参与肺泡修复。MSCs 和 MSC 衍生的因子可能刺激 BASCs 在 BPD 中发现的肺泡肺损伤修复和远端肺细胞上皮的恢复中发挥作用。这项工作突出了内源性肺干细胞在慢性肺部疾病修复中的潜在重要作用。
