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Stable Long-Term Culture of Human Distal Airway Stem Cells for Transplantation
Stem Cells International ( IF 4.3 ) Pub Date : 2021-09-17 , DOI: 10.1155/2021/9974635
Yueqing Zhou 1 , Yujia Wang 1, 2 , Dandan Li 1 , Ting Zhang 2 , Yu Ma 2 , Wei Zuo 1, 2, 3, 4
Affiliation  

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.

中文翻译:

用于移植的人类远端气道干细胞的长期稳定培养

存在 p63 + /Krt5 +的种群远端气道干细胞 (DASC) 静止地位于哺乳动物的气道基底上皮中,对损伤和气道上皮再生做出反应。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部分离的 DASC 的行为和特征,并探索其临床转化潜力。人类 DASC 通过支气管镜检查程序被刷掉,并在药物级条件下扩展。分析了它们在长期细胞培养中的表型稳定性,然后使用多种动物模型(包括啮齿动物和非人灵长类动物)进行安全性评估和致瘤性分析。人鼠肺模型的嵌合现象表明 DASC 谱系可以产生多种上皮类型,包括 I 型肺泡细胞和细支气管分泌细胞,以再生远端肺。综上所述,结果表明 DASC 移植可能是一种有前景的治疗方法,可以满足呼吸医学领域(包括 COVID-19 相关疾病)未满足的需求。
更新日期:2021-09-20
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