Infusion of Endothelial Progenitor Cells Accelerates Hematopoietic and Immune Reconstitution, and Ameliorates the Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation
Infusion of Endothelial Progenitor Cells Accelerates Hematopoietic and Immune Reconstitution, and Ameliorates the Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation
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DOI：
10.1007/s12013-012-9387-5
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发表时间：
2012-07
影响因子：
2.6
通讯作者：
L. Zeng;Chong Chen;G. Song;Zhi-ling Yan;Shi-juan Xu;Lu Jia;S. Ding;Jiang Cao;Wei Chen;Hai Cheng;Zhenyu Li;W. Sang;Lin Wang;Youping Li;K. Xu
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文献类型：
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作者：
L. Zeng;Chong Chen;G. Song;Zhi-ling Yan;Shi-juan Xu;Lu Jia;S. Ding;Jiang Cao;Wei Chen;Hai Cheng;Zhenyu Li;W. Sang;Lin Wang;Youping Li;K. Xu
造血干细胞移植(HSCT)会引起内皮细胞损伤，破坏造血微环境，导致各种并发症。我们推测，输注内皮祖细胞(EPC)可以改善内皮修复，促进造血重建，并减少与HSCT相关的并发症。C57BL6和BALB/c小鼠接受全身照射，然后输注C57BL6来源的骨髓(BM)细胞，同时或不同时输注C57BL6来源的内皮祖细胞。监测造血和免疫重建的时间进程和移植物抗宿主病(GVHD)的严重程度。此外，为了证实内皮祖细胞促进内皮细胞恢复，对HSCT小鼠进行了针对内皮的抗VE-钙粘附素抗体治疗。经内皮祖细胞处理的小鼠骨髓血管、细胞密度、造血干/祖细胞恢复加快，外周血淋巴细胞亚群数量增加，脾结构重建加快。EPC输注还改善了C57BL6-→和BALB/c allo-HSCT模型的移植物抗宿主病。全身注射抗VE-钙粘附素抗体显著延缓了注射内皮祖细胞小鼠的血液学和免疫重建。综上所述，我们的数据表明，输注内皮祖细胞可以促进造血和免疫重建，并减轻GVHD。这些发现进一步强调了微血管恢复、造血和免疫重建与移植物抗宿主病之间的关系。
Hematopoietic stem cells transplantation (HSCT) causes endothelial cell damage, disrupting hematopoietic microenviroment and leading to various complications. We hypothesized that infusion of endothelial progenitor cells (EPCs) may improve endothelium repair, facilitate hematopoietic reconstitution, and alleviate complications associated with HSCT. C57Bl6, and BALB/c mice received total body irradiation followed by infusion of C57Bl6-derived bone marrow (BM) cells, with or without concomitant infusion of C57Bl6-derived EPCs. The time course of hematopoietic and immune reconstitution and the severity of the graft-versus-host disease (GVHD) were monitored. Further, to confirm that EPCs promote endothelial cell recovery, HSCT mice were treated with anti-VE-cadherin antibody targeting the endothelium. The EPCs-treated mice exhibited accelerated recovery of BM vasculature, cellularity, hematopoietic stem and progenitor cell recovery, improved counts of lymphocyte subsets in peripheral blood, and facilitated spleen structure reconstruction. EPCs infusion also ameliorated the GVHD in the C57Bl6 → BALB/c allo-HSCT model. Systemic administration of anti-VE-cadherin antibody significantly delayed hematological and immune reconstitution in the EPCs-infused mice. In conclusion, our data demonstrate that infusion of EPCs augments the hematopoietic and immune reconstitution, and alleviates the GVHD. These findings further highlight the relationship between the microvascular recovery, hematopoietic and immune reconstitution, and the GVHD.