Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, University Hospital, Essen, Germany.
Department of Thoracic Surgery and Surgical Endoscopy, Ruhrlandklinik-University Clinic Essen, Essen, Germany.
Stem Cells Transl Med. 2021 Jan;10(1):128-143. doi: 10.1002/sctm.20-0191. Epub 2020 Aug 24.
Human lungs bear their own reservoir of endogenous mesenchymal stem cells (MSCs). Although described as located perivascular, the cellular identity of primary lung MSCs remains elusive. Here we investigated the vascular nature of lung-resident MSCs (LR-MSCs) using healthy human lung tissue. LR-MSCs predominately reside within the vascular stem cell niche, the so-called vasculogenic zone of adult lung arteries. Primary LR-MSCs isolated from normal human lung tissue showed typical MSC characteristics in vitro and were phenotypically and functionally indistinguishable from MSCs derived from the vascular wall of adult human blood vessels (VW-MSCs). Moreover, LR-MSCs expressed the VW-MSC-specific HOX code a characteristic to discriminate VW-MSCs from phenotypical similar cells. Thus, LR-MSC should be considered as VW-MSCs. Immunofluorescent analyses of non-small lung cancer (NSCLC) specimen further confirmed the vascular adventitia as stem cell niche for LR-MSCs, and revealed their mobilization and activation in NSCLC progression. These findings have implications for understanding the role of MSC in normal lung physiology and pulmonary diseases, as well as for the rational design of additional therapeutic approaches.
人体肺部拥有自身的内源性间充质干细胞（MSCs）储备。尽管这些细胞被描述为位于血管周围，但原发性肺 MSCs 的细胞特性仍难以捉摸。在这里，我们使用健康的人肺组织研究了肺驻留间充质干细胞（LR-MSCs）的血管特性。LR-MSCs 主要位于血管干细胞龛位，即成人肺动脉的所谓血管生成区。从正常人肺组织中分离出的原代 LR-MSCs 在体外表现出典型的 MSC 特征，并且在表型和功能上与从成人血管壁分离出的血管壁 MSC（VW-MSCs）没有区别。此外，LR-MSCs 表达 VW-MSC 特异性的 HOX 编码，这一特征可将 VW-MSCs 与表型相似的细胞区分开来。因此，LR-MSC 应被视为 VW-MSC。对非小细胞肺癌（NSCLC）标本的免疫荧光分析进一步证实了血管外膜是 LR-MSCs 的干细胞龛位，并揭示了它们在 NSCLC 进展中的动员和激活。这些发现对于理解 MSC 在正常肺生理学和肺部疾病中的作用以及合理设计额外的治疗方法具有重要意义。
