Ex vivo expanded human cord blood-derived hematopoietic progenitor cells induce lung growth and alveolarization in injured newborn lungs.

Ex vivo expanded human cord blood-derived hematopoietic progenitor cells induce lung growth and alveolarization in injured newborn lungs.
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DOI:
10.1186/1465-9921-14-37
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发表时间:
2013-03-23
影响因子:
5.8
通讯作者:
De Paepe ME
De Paepe ME
中科院分区:
医学2区
文献类型:
--
作者:
Mao Q;Chu S;Ghanta S;Padbury JF;De Paepe ME

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我们研究了绳索血液来源的CD34+造血祖细胞扩大的能力,可以在体内进行呼吸道上皮分化,并在体内植入和减轻肺泡破坏。 在存在生长因子和细胞因子(“碱性”培养基)的CD34+细胞中,研究了呼吸上皮分化,在补充地塞米松的一组中(“ DEX”)在纽伯恩(Newborn)的腹膜内被接种。肺部造成的肺部疾病,肺部生长和肺泡化后8周进行了研究。 在基本培养基中扩展的2/7 CD34+细胞分离株中,SP-C mRNA表达在DEX中膨胀,与细胞质SP-C免疫反应性和超微结构特征有关CD34+细胞与肺部暴露细胞处理的动物相关,增强了新鲜分离的CD34+细胞没有肺部生长或重塑的作用。 脐带血CD34+细胞可以诱导肺部肺部肺部的肺泡生长,这些促进生长的作用可能与旁氨核有关,或者持续的脐带血单核细胞的免疫调节作用,因为膨胀的细胞表现出有限的呼吸性上皮上皮thriventiation。
We investigated the capacity of expanded cord blood-derived CD34+ hematopoietic progenitor cells to undergo respiratory epithelial differentiation ex vivo, and to engraft and attenuate alveolar disruption in injured newborn murine lungs in vivo. Respiratory epithelial differentiation was studied in CD34+ cells expanded in the presence of growth factors and cytokines (“basic” medium), in one group supplemented with dexamethasone (“DEX”). Expanded or freshly isolated CD34+ cells were inoculated intranasally in newborn mice with apoptosis-induced lung injury. Pulmonary engraftment, lung growth and alveolarization were studied at 8 weeks post-inoculation. SP-C mRNA expression was seen in 2/7 CD34+ cell isolates expanded in basic media and in 6/7 isolates expanded in DEX, associated with cytoplasmic SP-C immunoreactivity and ultrastructural features suggestive of type II cell-like differentiation. Administration of expanding CD34+ cells was associated with increased lung growth and, in animals treated with DEX-exposed cells, enhanced alveolar septation. Freshly isolated CD34+ cells had no effect of lung growth or remodeling. Lungs of animals treated with expanded CD34+ cells contained intraalveolar aggregates of replicating alu-FISH-positive mononuclear cells, whereas epithelial engraftment was extremely rare. Expanded cord blood CD34+ cells can induce lung growth and alveolarization in injured newborn lungs. These growth-promoting effects may be linked to paracrine or immunomodulatory effects of persistent cord blood-derived mononuclear cells, as expanded cells showed limited respiratory epithelial transdifferentiation.
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