Stable Long-Term Culture of Human Distal Airway Stem Cells for Transplantation.

Stable Long-Term Culture of Human Distal Airway Stem Cells for Transplantation.
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用于移植的人远端气道干细胞的长期稳定培养

DOI:
10.1155/2021/9974635
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发表时间:
2021
影响因子:
4.3
通讯作者:
Zuo W
Zuo W
中科院分区:
医学3区
文献类型:
--
作者:
Zhou Y;Wang Y;Li D;Zhang T;Ma Y;Zuo W

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p63+/Krt 5+远端气道干细胞(distal airway stem cells,DASCs)在哺乳动物的气道基底上皮中存在,对损伤和气道上皮再生有反应。它们具有分化成多种肺细胞类型的能力,并且可以在损伤后重新填充上皮。目前的研究旨在进一步了解从患者肺中分离的DASC的行为和特征,并探索其临床转化潜力。通过支气管镜程序刷下人DASC,并在药物级条件下扩增。分析了它们在长期细胞培养中的表型稳定性,然后使用包括啮齿动物和非人灵长类动物在内的多种动物模型进行安全性评价和致瘤性分析。人-小鼠肺模型的嵌合体表明,DASC谱系可以产生多种上皮类型,包括I型肺泡细胞以及细支气管分泌细胞,以再生远端肺。综上所述,结果表明,DASC移植可能是一种有前途的治疗方法,可以满足呼吸内科(包括COVID-19相关疾病)的未满足需求。
There is a population of p63+/Krt5+ distal airway stem cells (DASCs) quiescently located in the airway basal epithelium of mammals, responding to injury and airway epithelial regeneration. They hold the ability to differentiate into multiple pulmonary cell types and can repopulate the epithelium after damage. The current study aims at gaining further insights into the behavior and characteristics of the DASCs isolated from the patient lung and exploring their clinical translational potential. Human DASCs were brushed off through the bronchoscopic procedure and expanded under the pharmaceutical-grade condition. Their phenotype stability in long-term cell culture was analyzed, followed by safety evaluation and tumorigenic analysis using multiple animal models including rodents and nonhuman primate. The chimerism of the human-mouse lung model indicated that DASC pedigrees could give rise to multiple epithelial types, including type I alveolar cells as well as bronchiolar secretory cells, to regenerate the distal lung. Taken together, the results suggested that DASC transplantation could be a promising therapeutic approach for unmet needs in respiratory medicine including the COVID-19-related diseases.
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