Cold storage of platelets in platelet additive solution maintains mitochondrial integrity by limiting initiation of apoptosis-mediated pathways
Cold storage of platelets in platelet additive solution maintains mitochondrial integrity by limiting initiation of apoptosis-mediated pathways
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DOI：
10.1111/trf.16185
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发表时间：
2020-12-08
期刊：
影响因子：
2.9
通讯作者：
Bynum, James A.
中科院分区：
文献类型：
--
作者：
Reddoch-Cardenas, Kristin M.;Peltier, Grant C.;Bynum, James A.
背景：血浆中血小板的冷藏可以维持止血功能，是一种有吸引力的替代室温血小板（rtp）的方法。我们最近的研究表明，冷藏血小板（CSPs）和rtp在储存5天后的功能差异与线粒体呼吸有关，并且血小板（PLT）添加剂溶液（PAS）中的CSPs可以维持至少15天的止血功能。研究设计和方法本研究验证了PAS冷藏通过减少PLT凋亡来保持线粒体完整性的假设。将血浆或PAS中的csp和rtp储存并分析长达15天的线粒体功能和完整性、线粒体相关mRNA转录物表达、凋亡蛋白和凋亡流式细胞术指标。结果CSP保存线粒体相关mRNA与基线水平相当，改善线粒体呼吸，最大限度地减少去极化至第15天。此外，CSPs对半胱天冬酶的诱导作用很小，保持了质膜的完整性，促凋亡Bax的表达也很低。在某些参数下，PAS中的储存似乎对rtp具有保护作用，并增强了csp的作用。结论线粒体功能和分子分析明确CSP启动与已有文献记载的RTP储存病变有明显不同。虽然目前血库在室温下的储存仅限于5至7天，但在PAS中冷藏和储存长达15天可能是增加库存和获得出血患者PLT止血支持的机会。
Background Cold storage of platelets in plasma maintains hemostatic function and is an attractive alternative to room temperature platelets (RTPs). We have recently shown that functional differences between cold-stored platelets (CSPs) and RTPs after 5-day storage are associated with mitochondrial respiration and that CSPs in platelet (PLT) additive solution (PAS) can maintain hemostatic function for at least 15 days.Study Design and Methods This study tested the hypothesis that cold storage in PAS preserves mitochondrial integrity by reducing PLT apoptosis. CSPs and RTPs in plasma or PAS were stored and assayed for up to 15 days for mitochondrial function and integrity, mitochondrial-associated mRNA transcript expression, apoptotic proteins, and apoptotic flow cytometry metrics.Results CSP preserved mitochondria-associated mRNA comparable to baseline levels, improved mitochondrial respiration, and minimized depolarization to Day 15. Additionally, CSPs had minimal induction of caspases, preservation of plasma membrane integrity, and low expression of pro-apoptotic Bax. Storage in PAS appeared to be protective for RTPs in some parameters and enhanced the effects of CSPs.Conclusion Mitochondrial function and molecular analyses defined CSP priming as distinctly different from the well-documented RTP storage lesion. While current blood bank storage at room temperature is limited to 5 to 7 days, refrigeration and storage in PAS for up to 15 days may represent an opportunity to enhance inventories and access to PLT hemostatic support for bleeding patients.