Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study.
Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study.
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DOI：
10.1186/2047-1440-3-19
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发表时间：
2014
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影响因子：
--
通讯作者：
Weiss DJ
中科院分区：
文献类型：
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作者：
La Francesca S;Ting AE;Sakamoto J;Rhudy J;Bonenfant NR;Borg ZD;Cruz FF;Goodwin M;Lehman NA;Taggart JM;Deans R;Weiss DJ
原发性移植物功能障碍（PGD）是肺移植术后早期发病和死亡的重要原因。改进的器官保存技术将减少导致PGD的缺血再灌注损伤（IRI）。成人骨髓来源的贴壁干细胞，包括间充质基质（干）细胞（MSC）和多能成体祖细胞（MAPC），具有有效的抗炎作用，因此，我们推测，在供体肺处理过程中，骨髓内给予MAPC将降低IRI。因此，该研究的目的是确定在长时间冷藏和随后再灌注的离体人肺外植体模型中，肺内MAPC滴注是否会减少肺损伤和炎症。四个未用于移植的供体肺经历8小时的冷藏（4°C）。复温约30分钟后，经支气管镜将非HLA匹配的同种异体MAPC（1 × 107 MAPC/肺）滴入左下叶（LLL），并将溶媒滴入右下叶（RLL）。然后肺灌注和机械通气4小时，随后评估组织学损伤和支气管肺泡灌洗液（BALF）和肺组织中的炎症标志物。与溶剂处理的RLL相比，所有LLL一致地显示出组织学和BALF炎症的显著降低。这些初步研究表明，在供体肺处理过程中使用非HLA匹配的同种异体MAPCs可以减少冷缺血诱导的肺损伤的标志物。本文的在线版本（doi：10.1186/2047-1440-3-19）包含补充材料，可供授权用户使用。
Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation. Improved organ preservation techniques will decrease ischemia-reperfusion injury (IRI) contributing to PGD. Adult bone marrow-derived adherent stem cells, including mesenchymal stromal (stem) cells (MSCs) and multipotent adult progenitor cells (MAPCs), have potent anti-inflammatory actions, and we thus postulated that intratracheal MAPC administration during donor lung processing would decrease IRI. The goal of the study was therefore to determine if intratracheal MAPC instillation would decrease lung injury and inflammation in an ex vivo human lung explant model of prolonged cold storage and subsequent reperfusion. Four donor lungs not utilized for transplant underwent 8 h of cold storage (4°C). Following rewarming for approximately 30 min, non-HLA-matched allogeneic MAPCs (1 × 107 MAPCs/lung) were bronchoscopically instilled into the left lower lobe (LLL) and vehicle comparably instilled into the right lower lobe (RLL). The lungs were then perfused and mechanically ventilated for 4 h and subsequently assessed for histologic injury and for inflammatory markers in bronchoalveolar lavage fluid (BALF) and lung tissue. All LLLs consistently demonstrated a significant decrease in histologic and BALF inflammation compared to vehicle-treated RLLs. These initial pilot studies suggest that use of non-HLA-matched allogeneic MAPCs during donor lung processing can decrease markers of cold ischemia-induced lung injury. The online version of this article (doi:10.1186/2047-1440-3-19) contains supplementary material, which is available to authorized users.