Increased chimerism of bronchial and alveolar epithelium in human lung allografts undergoing chronic injury
Increased chimerism of bronchial and alveolar epithelium in human lung allografts undergoing chronic injury
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DOI：
10.1016/s0002-9440(10)64281-2
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发表时间：
2003-05-01
影响因子：
6
通讯作者：
Kreipe, H
中科院分区：
文献类型：
--
作者：
Kleeberger, W;Versmold, A;Kreipe, H
在包括肝、心脏和肾在内的几种人类同种异体移植物中，已经显示出实质水平的嵌合体，其中整合的巨噬细胞来源的细胞最有可能来源于多能骨髓前体。我们研究了嵌合体是否也发生在肺的上皮结构内。为此目的，从7个移植的人肺同种异体移植物中获得存档组织活检。我们对靶结构进行了激光显微切割，随后进行了短串联重复序列分析，以检测分离细胞内的嵌合状态。我们发现，在所有研究的同种异体肺移植物中，支气管上皮细胞、II型肺细胞和邻近较大支气管的浆液粘液腺中均整合了肺源性细胞。定量分析显示，上皮结构显示慢性损伤的迹象，如鳞状上皮化生，表现出显着较高程度的嵌合体（24%对9.5%）。因此，我们的结论是，在人肺，上皮嵌合体至少发生在支气管，II型肺细胞，和浆液粘液支气管周围腺体。尽管先前在啮齿动物中的研究已经表明了移入的宿主来源的干细胞的骨髓来源，但是在本研究中，对骨髓移植患者（n = 3）的肺活检的分析不能证明这种描绘。受体细胞整合到慢性损伤的上皮结构中的增强的观察表明，肺外前体细胞能够促进肺再生。
Chimerism on the parenchymal level has been shown for several human allografts, including liver, heart, and kidney, with the integrated recipient-derived cells most likely originating from multipotent bone marrow precursors. We investigated whether chimerism also occurs within epithelial structures of the lung. For this purpose archival tissue biopsies from seven explanted human lung allografts were obtained. We performed laser microdissection of the target structures with subsequent short tandem repeat analysis to detect chimerism within the isolated cells. We found integration of recipient-derived cells in the bronchial epithelium, in type II pneumocytes and in seromucous glands lying adjacent to larger bronchi in all lung allografts studied. Quantitative analysis revealed that the epithelial structures displaying signs of chronic injury, such as squamous metaplasia, showed a markedly higher degree of chimerism (24% versus 9.5%). We therefore conclude that in human lungs, epithelial chimerism occurs at least within bronchi, type II pneumocytes, and seromucous peribronchial glands. Although a bone marrow origin of immigrating host-derived stem cells has been suggested by previous studies in rodents, analysis of lung biopsies from bone marrow-transplanted patients (n = 3) could not prove such delineation in this study. The observation of an enhanced integration of recipient cells into chronically damaged epithelial structures suggests that extrapulmonary precursor cells are able to contribute to pulmonary regeneration.