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异基因造血干细胞移植联合内皮祖细胞输注对骨髓炎性损伤的影响

[Effects of allogeneic hematopoietic stem cell transplantation in combination with infusion of endothelial progenitor cells on bone marrow inflammatory injury].

作者信息

Li W, Li M F, Zhao P P, Qiao J L, Xu K L, Zeng L Y

机构信息

Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221002, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2017 Apr 14;38(4):318-324. doi: 10.3760/cma.j.issn.0253-2727.2017.04.011.

DOI:10.3760/cma.j.issn.0253-2727.2017.04.011
PMID:28468094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7342716/
Abstract

To explore effects of allogeneic hematopoietic stem cell transplantation (HSCT) in combination with infusion of endothelial progenitor cells (EPC) on bone marrow inflammatory injury. 6-8 weeks BALB/c (H-2K(d)) mice after lethal dose of irradiation (TBI) were subjected to allogeneic bone marrow transplantation (BMT group) or co-transplantation of EPC (EPC group) . Samples of bone marrow cells of mice in each group on days 7,14,21,28 after transplantation were obtained to detect EPC cultural and cell chimeric rates by flow cytometer. Mice were sacrificed on days 7, 14, 21 and 28 post HSCT to analyze bone marrow pathology by H&E staining, the infiltration of macrophages and neutrophils by Western blot, validation expression levels of inflammatory complexes nlrp1、nlrp6 and its downstream molecules casepase-1 by Q-PCR and Western blot. Cell chimeric rate on day 7 after transplantation in EPC group[ (91.65±2.77) %] was significantly higher than in BMT group[ (83.69±1.26) %]. Alleviated osteomyelitis injury and inflammatory cell infiltration in EPC group were observed when compared with BMT mice. Also significant reductions of the levels of nlrp1、nlrp6、casepase-1 transcription complexes in EPC mice were noted when compared with BMT ones. Co-transplantation of HSC and EPC could alleviate inflammatory cell infiltration and activation of the complex to promote the repair of bone marrow.

摘要

探讨异基因造血干细胞移植(HSCT)联合输注内皮祖细胞(EPC)对骨髓炎性损伤的影响。对6-8周龄经致死剂量照射(TBI)后的BALB/c(H-2K(d))小鼠进行异基因骨髓移植(BMT组)或EPC共移植(EPC组)。在移植后第7、14、21、28天获取每组小鼠的骨髓细胞样本,通过流式细胞仪检测EPC培养率和细胞嵌合率。在HSCT后第7、14、21和28天处死小鼠,通过苏木精-伊红(H&E)染色分析骨髓病理,通过蛋白质印迹法检测巨噬细胞和中性粒细胞的浸润情况,通过实时定量聚合酶链反应(Q-PCR)和蛋白质印迹法验证炎性复合物nlrp1、nlrp6及其下游分子半胱天冬酶-1的表达水平。EPC组移植后第7天的细胞嵌合率[(91.65±2.77)%]显著高于BMT组[(83.69±1.26)%]。与BMT组小鼠相比,EPC组的骨髓炎损伤和炎性细胞浸润减轻。与BMT组小鼠相比,EPC组小鼠中nlrp1、nlrp6、半胱天冬酶-1转录复合物水平也显著降低。造血干细胞与EPC共移植可减轻炎性细胞浸润和复合物的激活,促进骨髓修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/e0a2c8060c18/cjh-38-04-318-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/166613d7ccef/cjh-38-04-318-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/be23b0a38249/cjh-38-04-318-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/505b8634763c/cjh-38-04-318-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/afbe4ab0c2e8/cjh-38-04-318-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/cd7285048b4d/cjh-38-04-318-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/e0a2c8060c18/cjh-38-04-318-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/166613d7ccef/cjh-38-04-318-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/be23b0a38249/cjh-38-04-318-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/505b8634763c/cjh-38-04-318-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/afbe4ab0c2e8/cjh-38-04-318-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/cd7285048b4d/cjh-38-04-318-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584c/7342716/e0a2c8060c18/cjh-38-04-318-g006.jpg

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本文引用的文献

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Bone marrow-derived endothelial progenitor cells promote hematopoietic reconstitution after hematopoietic stem cell transplantation.骨髓来源的内皮祖细胞促进造血干细胞移植后的造血重建。
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Endothelial injury, an intriguing effect of methotrexate and cyclophosphamide during hematopoietic stem cell transplantation in mice.内皮损伤,甲氨蝶呤和环磷酰胺在小鼠造血干细胞移植过程中产生的一种有趣效应。
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Bone marrow sinusoidal endothelial cells undergo nonapoptotic cell death and are replaced by proliferating sinusoidal cells in situ to maintain the vascular niche following lethal irradiation.骨髓窦状内皮细胞经历非凋亡性细胞死亡,并被原位增殖的窦状细胞取代,以在致死性照射后维持血管微环境。
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