Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model.
Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model.
复制标题
体外循环下间充质干细胞移植在幼年猪心脏模型中提供神经保护。
DOI：
10.1016/j.jacbts.2023.07.002
复制
发表时间：
2023-12
影响因子：
9.7
通讯作者：
Ishibashi, Nobuyuki
中科院分区：
文献类型：
--
作者：
Sarkislali, Kamil;Kobayashi, Kei;Saric, Nemanja;Maeda, Takuya;Henmi, Soichiro;Somaa, Fahad A.;Bansal, Ankush;Tu, Shao Ching;Leonetti, Camille;Hsu, Chao-Hsiung;Li, Jingang;Vyas, Pranav;Kawasawa, Yuka Imamura;Tu, Tsang-Wei;Wang, Paul C.;Hanley, Patrick J.;Hashimoto-Torii, Kazue;Frank, Joseph A.;Jonas, Richard A.;Ishibashi, Nobuyuki
关键词：
体外循环引起的氧化和炎症应激导致新生儿和婴儿大脑中小胶质细胞活化延长和皮质发育不良，从而导致先天性心脏病儿童的神经发育障碍。本研究使用我们的转化小猪模型发现，通过心肺转流输送间充质基质细胞可最大限度地减少小胶质细胞活化和神经元凋亡，随后改善新生儿心脏手术后的皮质发育不良和行为改变。转录组学分析表明，外泌体衍生的miRNA如miR-21- 5 p可能是间充质基质细胞输注后观察到的抑制凋亡和STAT 3介导的小胶质细胞活化的关键驱动因素。成功完成1期试验将需要设计新的基于细胞的方法来改善先天性心脏病儿童的神经发育障碍。体外循环（CPB）引起的氧化/炎症应激导致小胶质细胞活化延长和皮质发育不良，从而导致先天性心脏病（CHD）儿童的神经发育障碍。这项研究发现，通过CPB输送间充质基质细胞（MSC）可最大限度地减少小胶质细胞活化和神经元凋亡，随后改善新生儿心脏手术后的皮质发育不良和行为改变。此外，转录组学分析表明，外泌体衍生的miRNA可能是抑制细胞凋亡和STAT 3介导的小胶质细胞活化的关键驱动因素。我们的研究结果表明，心脏手术期间MSC治疗对改善CHD儿童的皮质发育不良和神经功能缺损具有显着的转化潜力。
Oxidative and inflammatory stresses attributable to cardiopulmonary bypass cause prolonged microglia activation and cortical dysmaturation in the neonatal and infant brain, thereby contributing to neurodevelopmental impairments in children with congenital heart disease. This study using our translational piglet model found that delivery of mesenchymal stromal cells via cardiopulmonary bypass minimizes microglial activation and neuronal apoptosis, with subsequent improvement of cortical dysmaturation and behavioral alteration after neonatal cardiac surgery. Transcriptomic analyses suggest that exosome-derived miRNAs such as miR-21-5p may be the key drivers of suppressed apoptosis and STAT3-mediated microglial activation observed following infusion of mesenchymal stromal cells. Successful completion of a phase 1 trial will be required to design new cell-based approaches for improvement of neurodevelopmental impairments in children with congenital heart disease. Oxidative/inflammatory stresses due to cardiopulmonary bypass (CPB) cause prolonged microglia activation and cortical dysmaturation, thereby contributing to neurodevelopmental impairments in children with congenital heart disease (CHD). This study found that delivery of mesenchymal stromal cells (MSCs) via CPB minimizes microglial activation and neuronal apoptosis, with subsequent improvement of cortical dysmaturation and behavioral alteration after neonatal cardiac surgery. Furthermore, transcriptomic analyses suggest that exosome-derived miRNAs may be the key drivers of suppressed apoptosis and STAT3-mediated microglial activation. Our findings demonstrate that MSC treatment during cardiac surgery has significant translational potential for improving cortical dysmaturation and neurological impairment in children with CHD.
登录
查看更多内容
影响因子：
4.6
作者：
Okamura, Toru;Ishibashi, Nobuyuki;Kumar, T. Susheel;Zurakowski, David;Iwata, Yusuke;Lidov, Hart G. W.;Jonas, Richard A.
通讯作者：
Jonas, Richard A.
影响因子：
29.7
作者：
Nayak D;Roth TL;McGavern DB
通讯作者：
McGavern DB
影响因子：
20.1
作者：
Morton PD;Ishibashi N;Jonas RA
通讯作者：
Jonas RA
影响因子：
5.3
作者：
Mitkari, Bhimashankar;Kerkela, Erja;Jolkkonen, Jukka
通讯作者：
Jolkkonen, Jukka
影响因子：
8.3
作者：
Moniche, Francisco;Gonzalez, Alejandro;Gil-Peralta, Alberto
通讯作者：
Gil-Peralta, Alberto