Effect of Intratracheal Administration of Adipose-derived Stromal Cells on Bleomycin-induced Lung Injury in a Rat Model.

M. Uji, A. Nakada, Tatsuo Nakamura, K. Hirata
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引用次数: 8

Abstract

BACKGROUND Mesenchymal stromal cells (MSCs) have been intensively investigated in regenerative medicine. Among the different types of MSCs, adipose tissue-derived stromal cells (ASCs) can be obtained with relatively less invasive techniques. Since ASC administration is a candidate strategy for the treatment of refractory diseases including pulmonary fibrosis, we investigated whether intratracheal injection of ASCs had therapeutic potential against bleomycin (BLM)-induced lung injury in rats. METHODS BLM was intratracheally administered to rats, and 1 week later ASCs were harvested. Two weeks after BLM treatment, ASCs or phosphate-buffered saline (PBS) were injected autologously into the rats via the trachea A semi-quantitative histological evaluation was conducted to assess the injured lungs, followed by cell tracing at 3 or 6 weeks after BLM instillation. RESULTS ASC administration did not affect the severity of lung damage on the third week after BLM exposure, but prevented further aggravation of the lung injury, as apparent on the sixth week. A fluorescent cell tracer revealed that the majority of ASCs did not appear to have penetrated inside the lung region injured by BLM on the third week after BLM instillation, but some of these cells sprouted deep into the thick distorted architecture of the injured lung on the sixth week after the BLM instillation. CONCLUSIONS The results of the present study suggest that ASCs may play a role in the prevention of ongoing aggravation of lung injury in the long term.
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气管内给药脂肪源性基质细胞对博莱霉素所致大鼠肺损伤模型的影响。
背景间充质基质细胞(MSCs)在再生医学中得到了广泛的研究。在不同类型的MSCs中,脂肪组织源性基质细胞(ASCs)可以通过相对较小的侵入性技术获得。由于ASC给药是治疗包括肺纤维化在内的难治性疾病的候选策略,我们研究了气管内注射ASC对博来霉素(BLM)诱导的大鼠肺损伤是否具有治疗潜力。方法大鼠经气管给药sblm, 1周后采集ASCs。BLM治疗2周后,经气管自体注射ASCs或磷酸盐缓冲盐水(PBS),半定量组织学评估损伤肺,并在BLM注射后3周或6周进行细胞示踪。结果在BLM暴露后第3周,asc给药不影响肺损伤的严重程度,但可以防止肺损伤进一步加重,这在第6周是明显的。荧光细胞示踪剂显示,在BLM注入后的第三周,大多数ASCs似乎没有渗透到BLM损伤的肺区域内,但在BLM注入后的第六周,其中一些ASCs深入到损伤肺的厚变形结构中。结论本研究结果表明,ASCs可能在长期预防肺损伤持续加重中发挥作用。
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