Autologous transplantation of endothelial progenitor cells to prevent multiple organ dysfunction syndromes in pig
Autologous transplantation of endothelial progenitor cells to prevent multiple organ dysfunction syndromes in pig
复制标题
自体移植内皮祖细胞预防猪多器官功能障碍综合征
DOI：
10.1097/ta.0b013e3182703420
复制
发表时间：
2013-02-01
影响因子：
3.4
通讯作者：
Fang Guoen
中科院分区：
文献类型：
--
作者：
Luo Tianhang;Wu Bo;Fang Guoen
研究发现，内皮祖细胞（endothelial progenitor cells, EPCs）在多器官功能障碍综合征（MODS）发展过程中数量和功能急剧下降，可能是多器官功能障碍综合征的主要发病机制。我们的目标是在MODS动物模型上进行EPCs的自体移植，探讨EPCs是否可以预防严重脓毒症引起的MODS。方法将60头猪随机分为3组：单纯失血性休克+复苏+内毒素血症组（MODS组）；失血性休克+复苏+内毒素血症后进行EPCs自体移植（移植组）；和对照组。移植组动物单核细胞经密度梯度离心分离体外扩增，内毒素血症24小时后，以5-羧基荧光素二乙酸琥珀酰酰酯标记的6代EPCs以1 × 107个/kg体重的密度自体移植。连续监测重要脏器功能，评价EPCs自体移植对MODS的影响。结果MODS组所有动物均发生MODS(100%)， 20只动物中有17只（85%）死于MODS；移植组MODS发病率为45% (9 / 20,p < 0.01)，死亡率为35% （7 / 20,p < 0.01）。移植组肺功能障碍发生率为40%，心功能障碍发生率为10%，肝功能障碍发生率为5%，肾功能障碍发生率为15%。EPCs自体移植后的心、肝、肾、肠、肺等重要脏器毛细血管密度均显著高于MODS组（p < 0.01）。结论自体内皮祖细胞移植可向损伤器官迁移，诱导血管生成，恢复血流，改善重要器官功能。可以预防MODS的发生，降低创伤和严重败血症的死亡率。内皮祖细胞的自体移植将是一种新的、基于细胞的、血管内皮靶向治疗MODS的策略。
BACKGROUND It was observed that the number and function of endothelial progenitor cells (EPCs) decreased sharply in the progression of multiple organ dysfunction syndrome (MODS), and it may be the main pathogenesis for MODS. We aim to perform autologous transplantation of EPCs on animal models of MODS to investigate whether EPCs might be used to prevent MODS caused by severe sepsis. METHODS A total of 60 pigs were randomly divided into three groups: subjected to hemorrhagic shock + resuscitation + endotoxemia only (MODS group); performed autologous transplantation of EPCs after hemorrhagic shock + resuscitation + endotoxemia (transplantation group); and control group. Mononuclear cells of animals of the transplantation group were isolated by density-gradient centrifugation for ex vivo expansion, and the six-passage EPCs labeled with 5-carboxyfluorescein diacetate succinimidyl ester were autologously transplanted at a density of 1 × 107 cells/kg body weight at the 24th hour after endotoxemia. The function of important organs was monitored continuously to assess the effects of autologous transplantation of EPCs on MODS. RESULTS All animals of the MODS group developed MODS (100%), and 17 (85%) of 20 animals died because of MODS; the incidence of MODS and mortality rate in the transplantation group were 45% (9 of 20 pigs; p < 0.01) and 35% (7 of 20 pigs; p < 0.01). In transplantation group, the incidence of pulmonary dysfunction, cardiac dysfunction, hepatosis, and renal dysfunction were 40%, 10%, 5%, and 15%, respectively. The capillary densities of important organs, including the heart, liver, kidney, intestine, and lung, after autologous transplantation of EPCs were significantly higher than those in the MODS group (p < 0.01). CONCLUSION Autologous transplantation of EPCs could migrate to injured organs and induce angiogenesis to restore blood flow that could improve the function of important organs. It could prevent the incidence of MODS and reduce mortality rate caused by trauma and severe sepsis. Autologous transplantation of EPCs would be a novel, cell-based, vascular endothelium–targeted therapeutic strategy for MODS.