Inflammation, Repair and Cancer of Respiratory Diseases (i-Respire), Fundació Institut d' Investigació Sanitària Illes Balears (IdISBa), 07120 Palma, Spain.
Estabulary, Scientific-Technical Services, Universitat de les Illes Balears (UIB), 07122 Palma, Spain.
Int J Mol Sci. 2023 Mar 18;24(6):5813. doi: 10.3390/ijms24065813.
COPD is a chronic lung disease that affects millions of people, declining their lung function and impairing their life quality. Despite years of research and drug approvals, we are still not capable of halting progression or restoring normal lung function. Mesenchymal stem cells (MSC) are cells with extraordinary repair capacity, and MSC-based therapy brings future hope for COPD treatment, although the best source and route of administration are unclear. MSC from adipose tissue (AD-MSC) represents an option for autologous treatment; however, they could be less effective than donor MSC. We compared in vitro behavior of AD-MSC from COPD and non-COPD individuals by migration/proliferation assay, and tested their therapeutic potential in an elastase mouse model. In addition, we tested intravenous versus intratracheal routes, inoculating umbilical cord (UC) MSC and analyzed molecular changes by protein array. Although COPD AD-MSC have impaired migratory response to VEGF and cigarette smoke, they were as efficient as non-COPD in reducing elastase-induced lung emphysema. UC-MSC reduced lung emphysema regardless of the administration route and modified the inflammatory profile in elastase-treated mice. Our data demonstrate equal therapeutic potential of AD-MSC from COPD and non-COPD subjects in the pre-clinical model, thus supporting their autologous use in disease.
慢性阻塞性肺疾病(COPD)是一种慢性肺部疾病,影响着数百万人,降低了他们的肺功能,损害了他们的生活质量。尽管经过多年的研究和药物批准,我们仍然无法阻止疾病进展或恢复正常的肺功能。间充质干细胞(MSC)是具有非凡修复能力的细胞,基于 MSC 的治疗为 COPD 的治疗带来了未来的希望,尽管最佳的来源和给药途径尚不清楚。脂肪组织(AD-MSC)来源的 MSC 代表了自体治疗的一种选择;然而,它们可能不如供体 MSC 有效。我们通过迁移/增殖测定比较了 COPD 和非 COPD 个体的 AD-MSC 的体外行为,并在弹性蛋白酶小鼠模型中测试了它们的治疗潜力。此外,我们测试了静脉内和气管内途径,接种脐带(UC)MSC,并通过蛋白质阵列分析分子变化。尽管 COPD AD-MSC 对 VEGF 和香烟烟雾的迁移反应受损,但它们在减轻弹性蛋白酶诱导的肺肺气肿方面与非 COPD 一样有效。UC-MSC 减轻了肺气肿,无论给药途径如何,并改变了弹性蛋白酶处理小鼠的炎症特征。我们的数据表明,来自 COPD 和非 COPD 受试者的 AD-MSC 在临床前模型中具有同等的治疗潜力,因此支持其在疾病中的自体使用。