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脂肪组织来源的基质细胞自体移植可改善肺气肿。

Autologous transplantation of adipose tissue-derived stromal cells ameliorates pulmonary emphysema.

作者信息

Shigemura N, Okumura M, Mizuno S, Imanishi Y, Nakamura T, Sawa Y

机构信息

Division of Cardiothoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

Am J Transplant. 2006 Nov;6(11):2592-600. doi: 10.1111/j.1600-6143.2006.01522.x.

Abstract

Adipose tissue is a useful tool for management of most complex cardiothoracic problems, including the reinforcement of damaged lungs, and adipose tissue-derived stromal cells (ASCs) have been suggested to secrete hepatocyte growth factor (HGF), a multipotent regenerative factor that contributes to the repair process after lung injury. The goal of this study was to demonstrate the therapeutic impact of autologous transplantation of ASCs through HGF supplementation for the enhancement of alveolar repair in a rat model of emphysema. ASCs were isolated from inguinal subcutaneous fat pads and characterized by flow cytometry. Cultured ASC were found to secrete significantly larger amounts of HGF (15 112 +/- 1628 pg per 10(6) cells) than other angiogenic factors. Transplantation of ASCs into elastase-treated emphysema models induced a significant increase in endogenous HGF expression in lung tissues with a small amount of increase in other organs, with the high levels lasting for up to 4 weeks after transplantation. Further, alveolar and vascular regeneration were significantly enhanced via inhibition of alveolar cell apoptosis, enhancement of epithelial cell proliferation and promotion of angiogenesis in pulmonary vasculature, leading to restoration of pulmonary function affected by emphysema. These data suggest that autologous ASC cell therapy may have a therapeutic potential for pulmonary emphysema, through inducing HGF expression selectively in injured lung tissues.

摘要

脂肪组织是处理大多数复杂心胸问题的有用工具,包括增强受损肺组织,并且有人提出脂肪组织来源的基质细胞(ASC)可分泌肝细胞生长因子(HGF),这是一种多能再生因子,有助于肺损伤后的修复过程。本研究的目的是通过补充HGF来证明自体移植ASC对肺气肿大鼠模型肺泡修复增强的治疗作用。从腹股沟皮下脂肪垫中分离出ASC,并通过流式细胞术进行表征。发现培养的ASC分泌的HGF(每10(6)个细胞15 112 +/- 1628 pg)比其他血管生成因子多得多。将ASC移植到经弹性蛋白酶处理的肺气肿模型中,可导致肺组织中内源性HGF表达显著增加,其他器官有少量增加,高水平可持续至移植后4周。此外,通过抑制肺泡细胞凋亡、增强上皮细胞增殖和促进肺血管生成,肺泡和血管再生显著增强,从而使受肺气肿影响的肺功能得以恢复。这些数据表明,自体ASC细胞疗法可能通过在受损肺组织中选择性诱导HGF表达而对肺气肿具有治疗潜力。

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