Mesenchymal Stem Cell-derived Extracellular Vesicles Prevent Experimental Bronchopulmonary Dysplasia Complicated By Pulmonary Hypertension.
Mesenchymal Stem Cell-derived Extracellular Vesicles Prevent Experimental Bronchopulmonary Dysplasia Complicated By Pulmonary Hypertension.
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间充质干细胞衍生的细胞外囊泡预防实验性支气管肺发育不良并发肺动脉高压。
DOI：
10.1093/stcltm/szac041
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发表时间：
2022-08-23
影响因子：
6
通讯作者：
Young, Karen
中科院分区：
文献类型：
--
作者：
Sharma, Mayank;Bellio, Michael A.;Benny, Merline;Kulandavelu, Shathiyah;Chen, Pingping;Janjindamai, Chawisa;Han, Chenxu;Chang, Liming;Sterling, Shanique;Williams, Kevin;Damianos, Andreas;Batlahally, Sunil;Kelly, Kaitlyn;Aguilar-Caballero, Daniela;Zambrano, Ronald;Chen, Shaoyi;Huang, Jian;Wu, Shu;Hare, Joshua M.;Schmidt, Augusto;Khan, Aisha;Young, Karen
关键词：
间充质干细胞(MSC)细胞外小泡(EVS)在临床前支气管肺发育不良和肺动脉高压(BPD-PH)模型中具有良好的作用。然而，效果的最佳来源、剂量、途径和持续时间尚不清楚。本研究的目的是(A)比较从Wharton‘s Jelly MSCs(WJ-MSCs)和骨髓(BM-MSCs)获得的GMP级EVS的疗效，(B)确定最佳剂量和给药途径，(C)评估其长期效果，以及(D)确定MSC EVS如何改变肺转录组。新生大鼠从出生后第1-14天开始暴露于常氧或高氧(85%O2)，分别给予(A)气管内(IT)BM或WJ-MSC EVS或安慰剂，(B)不同剂量的IT WJ-MSC EVS，或(C)IT或静脉注射(IV)WJ-MSC EVS。在14个月或3个月时对大鼠进行评估。早期给予IT、BM-MSC或WJ-MSC EVS对高氧暴露大鼠的肺结构和PH值有相似的有益影响。然而，WJ-MSC EVS在心脏重塑方面有更好的效果。低、中、高剂量WJ-MSC EVS具有相似的心肺再生效应。它和静脉注射WJ-MSC EVS类似地改善高氧大鼠的血管密度和降低PH值。对WJ-MSC EV处理大鼠差异表达的转录本进行的基因集浓缩分析表明，诱导的转录本与血管生成相关。长期研究表明，早期单次MSC EV给药3个月后有肺血管保护作用。总之，我们的发现具有重要的翻译意义，因为它为BPD-PH的MSC-EVS的最佳来源、剂量、途径、作用机制和持续时间提供了关键的洞察力。
Mesenchymal stem cell (MSC) extracellular vesicles (EVs) have beneficial effects in preclinical bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) models. The optimal source, dosing, route, and duration of effects are however unknown. The objectives of this study were to (a) compare the efficacy of GMP-grade EVs obtained from Wharton’s Jelly MSCs (WJ-MSCs) and bone marrow (BM-MSCs), (b) determine the optimal dosing and route of administration, (c) evaluate its long-term effects, and (d) determine how MSC EVs alter the lung transcriptome. Newborn rats exposed to normoxia or hyperoxia (85% O2) from postnatal day (P)1-P14 were given (a) intra-tracheal (IT) BM or WJ-MSC EVs or placebo, (b) varying doses of IT WJ-MSC EVs, or (c) IT or intravenous (IV) WJ-MSC EVs on P3. Rats were evaluated at P14 or 3 months. Early administration of IT BM-MSC or WJ-MSC EVs had similar beneficial effects on lung structure and PH in hyperoxia-exposed rats. WJ-MSC EVs however had superior effects on cardiac remodeling. Low, medium, and high dose WJ-MSC EVs had similar cardiopulmonary regenerative effects. IT and IV WJ-MSC EVs similarly improved vascular density and reduced PH in hyperoxic rats. Gene-set enrichment analysis of transcripts differentially expressed in WJ-MSC EV-treated rats showed that induced transcripts were associated with angiogenesis. Long-term studies demonstrated that a single early MSC EV dose has pulmonary vascular protective effects 3 months after administration. Together, our findings have significant translational implications as it provides critical insight into the optimal source, dosing, route, mechanisms of action, and duration of effects of MSC-EVs for BPD-PH.
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影响因子：
16.6
作者：
Soler Artigas M;Wain LV;Miller S;Kheirallah AK;Huffman JE;Ntalla I;Shrine N;Obeidat M;Trochet H;McArdle WL;Alves AC;Hui J;Zhao JH;Joshi PK;Teumer A;Albrecht E;Imboden M;Rawal R;Lopez LM;Marten J;Enroth S;Surakka I;Polasek O;Lyytikäinen LP;Granell R;Hysi PG;Flexeder C;Mahajan A;Beilby J;Bossé Y;Brandsma CA;Campbell H;Gieger C;Gläser S;González JR;Grallert H;Hammond CJ;Harris SE;Hartikainen AL;Heliövaara M;Henderson J;Hocking L;Horikoshi M;Hutri-Kähönen N;Ingelsson E;Johansson Å;Kemp JP;Kolcic I;Kumar A;Lind L;Melén E;Musk AW;Navarro P;Nickle DC;Padmanabhan S;Raitakari OT;Ried JS;Ripatti S;Schulz H;Scott RA;Sin DD;Starr JM;UK BiLEVE;Viñuela A;Völzke H;Wild SH;Wright AF;Zemunik T;Jarvis DL;Spector TD;Evans DM;Lehtimäki T;Vitart V;Kähönen M;Gyllensten U;Rudan I;Deary IJ;Karrasch S;Probst-Hensch NM;Heinrich J;Stubbe B;Wilson JF;Wareham NJ;James AL;Morris AP;Jarvelin MR;Hayward C;Sayers I;Strachan DP;Hall IP;Tobin MD
通讯作者：
Tobin MD
DOI：
10.1164/rccm.200902-0242oc
发表时间：
2009-12-01
影响因子：
24.7
作者：
Aslam, Muhammad;Baveja, Rajiv;Kourembanas, Stella
通讯作者：
Kourembanas, Stella
影响因子：
2.5
作者：
Bancalari, Eduardo;Jain, Deepak
通讯作者：
Jain, Deepak
影响因子：
5.2
作者：
Kern, Susanne;Eichler, Hermann;Bieback, Karen
通讯作者：
Bieback, Karen
影响因子：
4.6
作者：
Leeman, Kristen T.;Pessina, Patrizia;Kim, Carla F.
通讯作者：
Kim, Carla F.