Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects
Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects
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DOI：
10.1073/pnas.1432929100
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发表时间：
2003-07-08
影响因子：
11.1
通讯作者：
Phinney, DG
中科院分区：
文献类型：
--
作者：
Ortiz, LA;Gambelli, F;Phinney, DG
以前，我们描述了一种可靠的方法，基于免疫耗竭分离小鼠骨髓间充质干细胞（MSC），并表明，颅内移植后，细胞迁移到整个前脑和小脑，并通过神经细胞的命运。在这里，我们全身管理MSC纯化的免疫耗竭雄性博莱霉素（BLM）耐药BALB/c小鼠到女性BLM敏感的C57 BL/6受体和定量植入水平在肺实时PCR。在对照组小鼠中，雄性DNA占总肺DNA的2.21 × 10（-5）%，但在MSC移植前暴露于BLM的动物中增加了23倍（P = 0.05）。荧光原位杂交显示，移植的雄性细胞定位于BLM诱导的损伤区域，并表现出上皮样形态。此外，从移植受体的肺中纯化II型上皮细胞导致与整个肺组织相比3倍富集的雄性供体来源的细胞。暴露于BLM后立即给予MSC也显著降低了BLM诱导的炎症和肺组织内胶原沉积的程度。总的来说，这些研究表明，鼠MSC响应于损伤而归巢至肺，采用上皮样表型，并减少用BLM攻击的小鼠的肺组织中的炎症和胶原沉积。
Previously we described a reliable method based on immunodepletion for isolating mesenchymal stem cells (MSCs) from murine bone marrow and showed that, after intracranial transplantation, the cells migrated throughout forebrain and cerebellum and adopted neural cell fates. Here we systemically administered MSCs purified by immunodepletion from male bleomycin (BLM)-resistant BALB/c mice into female BLM-sensitive C57BL/6 recipients and quantified engraftment levels in lung by real-time PCR. Male DNA accounted for 2.21 x 10(-5)% of the total lung DNA in control-treated mice but was increased 23-fold (P = 0.05) in animals exposed to BLM before MSC transplantation. Fluorescence in situ hybridization revealed that engrafted male cells were localized to areas of BLM-induced injury and exhibited an epithelium-like morphology. Moreover, purification of type II epithelial cells from the lungs of transplant recipients resulted in a 3-fold enrichment of male, donor-derived cells as compared with whole lung tissue. MSC administration immediately after exposure to BLM also significantly reduced the degree of BLM-induced inflammation and collagen deposition within lung tissue. Collectively, these studies demonstrate that murine MSCs home to lung in response to injury, adopt an epithelium-like phenotype, and reduce inflammation and collagen deposition in lung tissue of mice challenged with BLM.