Broekman Winifred, Roelofs Helene, Zarcone Maria C, Taube Christian, Stolk Jan, Hiemstra Pieter S
Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Dept of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
ERJ Open Res. 2016 Jun 28;2(2). doi: 10.1183/23120541.00045-2015. eCollection 2016 Apr.
Autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) are evaluated for clinical use in chronic obstructive pulmonary disease (COPD) patients, but it is unclear whether COPD affects BM-MSCs. To investigate this, BM-MSCs from nine COPD patients and nine non-COPD age-matched controls were compared with regard to immunophenotype, growth and differentiation potential, and migration capacity. Other functional assays included the response to pro-inflammatory stimuli and inducers of the nuclear factor (erythroid derived 2)-like 2 antioxidant response element (Nrf2-ARE) pathway, and effects on NCI-H292 airway epithelial cells. No significant differences were observed in terms of morphology, proliferation and migration, except for increased adipocyte differentiation potential in the COPD group. Both groups were comparable regarding mRNA expression of growth factors and inflammatory mediators, and in their potential to induce mRNA expression of epidermal growth factor receptor ligands in NCI-H292 airway epithelial cells. MSCs from COPD patients secreted more interleukin-6 in response to pro-inflammatory stimuli. Activation of the Nrf2-ARE pathway resulted in a comparable induction of mRNA expression of four target genes, but the expression of the NAD(P)H:quinone oxidoreductase 1 gene was lower in MSCs from COPD patients. The observation that MSCs from COPD patients are phenotypically and functionally comparable to those from non-COPD controls implies that autologous MSCs can be considered for use in the setting of clinical trials as a treatment for COPD.
自体骨髓间充质基质细胞（BM-MSCs）已在慢性阻塞性肺疾病（COPD）患者中进行临床应用评估，但尚不清楚COPD是否会影响BM-MSCs。为了研究这一问题，对9例COPD患者和9例年龄匹配的非COPD对照者的BM-MSCs在免疫表型、生长和分化潜能以及迁移能力方面进行了比较。其他功能测定包括对促炎刺激和核因子（红细胞衍生2）样2抗氧化反应元件（Nrf2-ARE）途径诱导剂的反应，以及对NCI-H292气道上皮细胞的影响。除COPD组脂肪细胞分化潜能增加外，在形态、增殖和迁移方面未观察到显著差异。两组在生长因子和炎症介质的mRNA表达以及诱导NCI-H292气道上皮细胞中表皮生长因子受体配体mRNA表达的潜能方面具有可比性。COPD患者的MSCs对促炎刺激分泌更多白细胞介素-6。Nrf2-ARE途径的激活导致四个靶基因mRNA表达的诱导相当，但COPD患者的MSCs中NAD(P)H:醌氧化还原酶1基因的表达较低。COPD患者的MSCs在表型和功能上与非COPD对照者的MSCs相当这一观察结果表明，自体MSCs可考虑用于临床试验中作为COPD的一种治疗方法。
