Park Jin Soo, Kim Hyun Kuk, Kang Eun Young, Cho RyeonJin, Oh Yeon Mok
Asan Institute for Life Sciences, Seoul, Korea.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea.
Tuberc Respir Dis (Seoul). 2019 Apr;82(2):158-165. doi: 10.4046/trd.2018.0044. Epub 2018 Sep 28.
A recent study reported that mesenchymal stem cells possess potential cellular therapeutic properties for treating patients with chronic obstructive pulmonary disease, which is characterized by emphysema. We examined the potential therapeutic effect of Wharton's Jelly-derived mesenchymal stem cells (WJMSCs), following pretreatment with pioglitazone, in lung regeneration mouse emphysema models.
We used two mouse emphysema models, an elastase-induced model and a cigarette smoke-induced model. We intravenously injected WJMSCs (1×10⁴/mouse) to mice, pretreated or not, with pioglitazone for 7 days. We measured the emphysema severity by mean linear intercepts (MLI) analysis using lung histology.
Pioglitazone pretreated WJMSCs (pioWJMSCs) were associated with greater lung regeneration than non-augmented WJMSCs in the two mouse emphysema models. In the elastase-induced emphysema model, the MLIs were 59.02±2.42 μm (n=6), 72.80±2.87 μm (n=6), for pioWJMSCs injected mice, and non-augmented WJMSCs injected mice, respectively (p<0.01). Both pioWJMSCs and non-augmented WJMSCs showed regenerative effects in the cigarette smoke emphysema model (MLIs were 41.25±0.98 [n=6] for WJMSCs and38.97±0.61 μm [n=6] for pioWJMSCs) compared to smoking control mice (51.65±1.36 μm, n=6). The mean improvement of MLI appeared numerically better in pioWJMSCs than in non-augmented WJMSCs injected mice, but the difference did not reach the level of statistical significance (p=0.071).
PioWJMSCs may produce greater lung regeneration, compared to non-augmented WJMSCs, in a mouse emphysema model.
最近一项研究报道,间充质干细胞具有治疗慢性阻塞性肺疾病患者的潜在细胞治疗特性,慢性阻塞性肺疾病以肺气肿为特征。我们在肺再生小鼠肺气肿模型中研究了用吡格列酮预处理后的沃顿胶源性间充质干细胞(WJMSCs)的潜在治疗效果。
我们使用了两种小鼠肺气肿模型,一种是弹性蛋白酶诱导模型和一种香烟烟雾诱导模型。我们给小鼠静脉注射WJMSCs(1×10⁴/只小鼠),这些小鼠用或不用吡格列酮预处理7天。我们通过使用肺组织学的平均线性截距(MLI)分析来测量肺气肿严重程度。
在两种小鼠肺气肿模型中,与未增强的WJMSCs相比,吡格列酮预处理的WJMSCs(pioWJMSCs)与更大程度的肺再生相关。在弹性蛋白酶诱导的肺气肿模型中,注射pioWJMSCs的小鼠和注射未增强的WJMSCs的小鼠的MLI分别为59.02±2.42μm(n = 6)、72.80±2.87μm(n = 6)(p<0.01)。与吸烟对照小鼠(51.65±1.36μm,n = 6)相比,pioWJMSCs和未增强的WJMSCs在香烟烟雾肺气肿模型中均显示出再生效果(WJMSCs的MLI为41.25±0.98[n = 6],pioWJMSCs的MLI为38.97±0.61μm[n = 6])。注射pioWJMSCs的小鼠的MLI平均改善在数值上似乎比注射未增强的WJMSCs的小鼠更好,但差异未达到统计学显著水平(p = 0.071)。
在小鼠肺气肿模型中,与未增强的WJMSCs相比,pioWJMSCs可能产生更大程度的肺再生。