Intranasal delivery of human umbilical cord Wharton's jelly mesenchymal stromal cells restores lung alveolarization and vascularization in experimental bronchopulmonary dysplasia
Intranasal delivery of human umbilical cord Wharton's jelly mesenchymal stromal cells restores lung alveolarization and vascularization in experimental bronchopulmonary dysplasia
复制标题
DOI：
10.1002/sctm.18-0273
复制
发表时间：
2019-11-27
影响因子：
6
通讯作者：
Ahuja, Sunil
中科院分区：
文献类型：
--
作者：
Moreira, Alvaro;Winter, Caitlyn;Ahuja, Sunil
支气管肺发育不良(BPD)是一种破坏性的肺部疾病，发生于暴露于长时间机械通气和补充氧气的早产儿。严重的发病率和死亡率与这种昂贵的疾病有关，有效的治疗方法有限。间充质干细胞是一种多能细胞，可通过分泌旁分泌因子修复受损组织，恢复受损肺上皮和内皮的功能和完整性。大多数临床前研究表明，MSCs对BPD的治疗效果是通过气管内或静脉给药的。本研究的目的是研究经鼻腔给药的人脐带组织来源的间充质干细胞的可行性和有效性。分离、鉴定人脐组织间充质干细胞，以50万个/20亩L细胞接种于高氧诱导的BPD大鼠模型。在接受MSC治疗的动物中，肺泡化、血管化和肺血管重塑得到恢复。基因和蛋白质分析表明，MSCs的有益作用部分归因于针对血管生成、免疫调节、伤口愈合和细胞存活的协同努力。这些发现具有临床意义，因为发展为BPD的新生儿改变了肺泡发育，肺血管形成减少和慢性炎症，所有这些都导致组织愈合受损。本研究首次报道了脐带Wharton‘s凝胶MSCs鼻腔内移植治疗实验性BPD是可行的、非侵入性的，是一种可能具有临床适用性的有效途径。
Bronchopulmonary dysplasia (BPD) is a devastating lung condition that develops in premature newborns exposed to prolonged mechanical ventilation and supplemental oxygen. Significant morbidity and mortality are associated with this costly disease and effective therapies are limited. Mesenchymal stem/stromal cells (MSCs) are multipotent cells that can repair injured tissue by secreting paracrine factors known to restore the function and integrity of injured lung epithelium and endothelium. Most preclinical studies showing therapeutic efficacy of MSCs for BPD are administered either intratracheally or intravenously. The purpose of this study was to examine the feasibility and effectiveness of human cord tissue-derived MSC administration given via the intranasal route. Human umbilical cord tissue MSCs were isolated, characterized, and given intranasally (500 000 cells per 20 mu L) to a hyperoxia-induced rat model of BPD. Lung alveolarization, vascularization, and pulmonary vascular remodeling were restored in animals receiving MSC treatment. Gene and protein analysis suggest the beneficial effects of MSCs were attributed, in part, to a concerted effort targeting angiogenesis, immunomodulation, wound healing, and cell survival. These findings are clinically significant, as neonates who develop BPD have altered alveolar development, decreased pulmonary vascularization and chronic inflammation, all resulting in impaired tissue healing. Our study is the first to report the intranasal delivery of umbilical cord Wharton's jelly MSCs in experimental BPD is feasible, noninvasive, and an effective route that may bear clinical applicability.