Harvest tissue source does not alter the protective power of stromal cell therapy after intestinal ischemia and reperfusion injury.
Harvest tissue source does not alter the protective power of stromal cell therapy after intestinal ischemia and reperfusion injury.
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DOI：
10.1016/j.jss.2016.05.006
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发表时间：
2016-08
影响因子：
2.2
通讯作者：
Markel, Troy A.
中科院分区：
文献类型：
--
作者：
Jensen, Amanda R.;Manning, Morenci M.;Khaneki, Sina;Drucker, Natalie A.;Markel, Troy A.
关键词：
骨髓间充质干细胞移植可能是治疗肠缺血的一种新方法。然而，最佳的基质细胞来源，可以产生最大的保护损伤后，尚未确定。我们假设：1）MSC将增加存活和肠系膜灌注，保护肠组织结构，并限制肠缺血和再灌注损伤（I/R）后的炎症，和2）从不同组织来源收获的MSC将具有I/R后对肠的等效保护特性。将成年雄性小鼠麻醉并进行中线剖腹术。将肠取出，确定小肠肠系膜根，并使用激光多普勒成像（LDI）确定基线肠灌注。通过用非挤压钳暂时闭塞上级肠系膜动脉60分钟来建立肠缺血。在局部缺血后，移除夹钳并使肠恢复。在腹部闭合之前，将250μl磷酸盐缓冲盐水（PBS）载体中的2 × 106人脐带（USCs）、骨髓（BMSC）来源的MSC或角质形成细胞注射到腹膜中。允许动物恢复12或24小时（灌注、组织学、炎症研究）或7天（存活研究）。使用对数秩检验分析存活数据。灌注表示为基线的百分比，并且使用单因素ANOVA和学生t检验分析12和24小时数据。使用Mann-Whitney-U检验比较非参数数据。p值小于0.05具有显著性。I/R后7天，所有MSC的存活率均增加，并且优于载体或角质形成细胞（P<0.05），这是上级的。在损伤后12和24小时，所有MSC均增加肠系膜灌注超过赋形剂（P<0.05）。在损伤后24小时，与角质形成细胞相比，所有MSC提供了更好的上级灌注（P<0.05）。各组间充质干细胞移植均能改善肠缺血再灌注后的组织学改变（P<0.05）。应用MSC后，多种促炎趋化因子下调，表明MSC治疗后炎症反应降低。在肠I/R后移植MSC，无论来源组织如何，均显著增加存活率和肠系膜灌注，同时限制肠损伤和炎症。需要进一步的研究来确定这些细胞用于促进损伤后改善结果的机制。
Transplantation of mesenchymal stromal cells (MSCs) may be a novel treatment for intestinal ischemia. The optimal stromal cell source that could yield maximal protection following injury, however, has not been identified. We hypothesized that: 1) MSCs would increase survival and mesenteric perfusion, preserve intestinal histological architecture, and limit inflammation following intestinal ischemia and reperfusion injury (I/R), and 2) MSCs harvested from different sources of tissue would have equivalent protective properties to the intestine following I/R. Adult male mice were anesthetized and a midline laparotomy performed. The intestines were eviscerated, the small bowel mesenteric root identified, and baseline intestinal perfusion was determined using Laser Doppler Imaging (LDI). Intestinal ischemia was established by temporarily occluding the superior mesenteric artery for 60 minutes with a non-crushing clamp. Following ischemia, the clamp was removed and the intestines were allowed to recover. Prior to abdominal closure, 2 × 106 human umbilical (USCs), bone-marrow (BMSCs) derived MSCs, or keratinocytes in 250μl of phosphate-buffered saline (PBS) vehicle were injected into the peritoneum. Animals were allowed to recover for 12 or 24 hours (perfusion, histology, inflammatory studies), or 7 days (survival studies). Survival data was analyzed using log rank test. Perfusion was expressed as percentage of baseline and 12 and 24 hour data was analyzed using one way ANOVA and student’s t-test. Non parametric data was compared using Mann-Whitney-U test. A p-value of less than 0.05 was significant. All MSCs increased seven day survival following I/R and were superior to vehicle or keratinocytes (P<0.05). All MSCs increased mesenteric perfusion above vehicle at 12 and 24 hours following injury (P<0.05). All MSCs provided superior perfusion compared to keratinocytes at 24 hours post-injury (P<0.05). Administration of each MSC line improved intestinal histology after I/R (P<0.05). Multiple pro-inflammatory chemokines were down-regulated following application of MSCs suggesting a decreased inflammatory response following MSC therapy. Transplantation of MSCs following intestinal I/R, irrespective of source tissue, significantly increases survival and mesenteric perfusion while limiting intestinal damage and inflammation. Further studies are needed to identify the mechanism that these cells utilize to promote improved outcomes following injury.
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影响因子：
3.7
作者：
Mikami S;Nakashima A;Nakagawa K;Maruhashi T;Iwamoto Y;Kajikawa M;Matsumoto T;Kihara Y;Chayama K;Noma K;Ochi M;Nishimura M;Tsuji K;Kato Y;Goto C;Higashi Y
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Higashi Y
影响因子：
3.7
作者：
Jiang H;Qu L;Dou R;Lu L;Bian S;Zhu W
通讯作者：
Zhu W
影响因子：
4.3
作者：
Shen, Zhong-Yang;Zhang, Jing;Zheng, Wei-Ping
通讯作者：
Zheng, Wei-Ping
影响因子：
5.2
作者：
Kern, Susanne;Eichler, Hermann;Bieback, Karen
通讯作者：
Bieback, Karen
影响因子：
3.1
作者：
Luo, Cong-juan;Zhang, Fu-jian;Chen, Xiang-mei
通讯作者：
Chen, Xiang-mei