Comparative Effects of Bone Marrow-derived Versus Umbilical Cord Tissue Mesenchymal Stem Cells in an Experimental Model of Bronchopulmonary Dysplasia.

Comparative Effects of Bone Marrow-derived Versus Umbilical Cord Tissue Mesenchymal Stem Cells in an Experimental Model of Bronchopulmonary Dysplasia.
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DOI:
10.1093/stcltm/szab011
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发表时间:
2022-03-17
影响因子:
6
通讯作者:
Young KC
Young KC
中科院分区:
医学2区
文献类型:
--
作者:
Benny M;Courchia B;Shrager S;Sharma M;Chen P;Duara J;Valasaki K;Bellio MA;Damianos A;Huang J;Zambrano R;Schmidt A;Wu S;Velazquez OC;Hare JM;Khan A;Young KC

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支气管肺发育不良(BPD)是早产儿的一种危及生命的疾病,几乎没有有效的治疗方法。间充质干细胞或基质细胞(MSC)是一种有前途的治疗策略BPD。然而,用于BPD预防的理想MSC来源是未知的。本研究的目的是比较从骨髓(BM)和脐带组织(UCT)中获得的MSC在实验性BPD模型中的再生效果。在体外,与BM-MSC相比,UCT-MSC表现出更大的增殖和抗炎细胞因子的表达。用UCT-MSC条件培养基(CM)孵育的肺上皮细胞在划痕损伤后具有更好的伤口愈合。UCT-MSC CM和BM-MSC CM对高氧暴露的肺微血管内皮细胞具有相似的促血管生成作用。在体内,从出生后第1天(P)至第21天暴露于常氧或高氧(85% O2)的新生大鼠在P3气管内(IT)给予BM或UCT-MSC(1 × 106个细胞/50 μL)或安慰剂(PL)。高氧PL治疗的大鼠具有显著的肺泡简化、肺血管密度降低、肺血管重构和肺部炎症。相比之下,BM-MSC和UCT-MSC的施用显著改善肺泡结构、肺血管生成、肺血管重塑和肺部炎症。然而,与BM-MSC治疗组相比,UCT-MSC高氧暴露大鼠在肺泡化的一些形态测量指标和较少的肺巨噬细胞浸润方面有更大的改善。总之,这些发现表明BM-MSC和UCT-MSC在实验BPD中具有显著的肺再生作用,但UCT-MSC抑制肺巨噬细胞浸润并在更大程度上促进肺上皮细胞愈合。
Bronchopulmonary dysplasia (BPD) is a life-threatening condition in preterm infants with few effective therapies. Mesenchymal stem or stromal cells (MSCs) are a promising therapeutic strategy for BPD. The ideal MSC source for BPD prevention is however unknown. The objective of this study was to compare the regenerative effects of MSC obtained from bone marrow (BM) and umbilical cord tissue (UCT) in an experimental BPD model. In vitro, UCT-MSC demonstrated greater proliferation and expression of anti-inflammatory cytokines as compared to BM-MSC. Lung epithelial cells incubated with UCT-MSC conditioned media (CM) had better-wound healing following scratch injury. UCT-MSC CM and BM-MSC CM had similar pro-angiogenic effects on hyperoxia-exposed pulmonary microvascular endothelial cells. In vivo, newborn rats exposed to normoxia or hyperoxia (85% O2) from postnatal day (P) 1 to 21 were given intra-tracheal (IT) BM or UCT-MSC (1 × 106 cells/50 μL), or placebo (PL) on P3. Hyperoxia PL-treated rats had marked alveolar simplification, reduced lung vascular density, pulmonary vascular remodeling, and lung inflammation. In contrast, administration of both BM-MSC and UCT-MSC significantly improved alveolar structure, lung angiogenesis, pulmonary vascular remodeling, and lung inflammation. UCT-MSC hyperoxia-exposed rats however had greater improvement in some morphometric measures of alveolarization and less lung macrophage infiltration as compared to the BM-MSC-treated group. Together, these findings suggest that BM-MSC and UCT-MSC have significant lung regenerative effects in experimental BPD but UCT-MSC suppresses lung macrophage infiltration and promotes lung epithelial cell healing to a greater degree.
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