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人脐带血源基质细胞共移植增强了辐照 BABL/c 小鼠的造血重建和植入。

Cotransplantation of human umbilical cord blood-derived stromal cells enhances hematopoietic reconstitution and engraftment in irradiated BABL/c mice.

机构信息

Department of Hematology, Second Affiliated Hospital, The Third Military Medical University, Chongqing, China.

出版信息

Cancer Biol Ther. 2011 Jan 1;11(1):84-94. doi: 10.4161/cbt.11.1.13956.

Abstract

Our previous study demonstrated that human umbilical cord blood-derived stromal cells (hUCBDSCs) support the growth of hematopoietic stem cells, and promote the expansion of colony-forming units of megakaryocyte (CFU-Mk) even more efficiently than human bone marrow stromal cells (hBMSCs). Given the unique role of hUCBDSCs in megakaryocytopoiesis in vitro, in this follow up study, we further investigated their effects in vivo on hematopoiesis in the setting of hematopoietic stem cell (HSC) transplants. After infusing hematopoietic cells alone or together with either hUCBDSCs or hBMSCs into lethally irradiated BABL/c mice, we examined the engraftment of human CD45+ cells in the mouse bone marrow with flow cytometry, observed the survival rate of irradiated mice, obtained blood counts and bone marrow biopsies at different time points post-transplant, and assessed colony forming and the homing efficiency of hematopoietic cells. By comparing HSC transplantation with or without stromal cells, we show here that hUCBDSCs efficiently promote the homing of hematopoietic cells to the marrow and enhance the engraftment after cotransplantation. They also promote hematopoietic reconstitution, particularly of the megakaryocytic lineage, and restore the impaired stromal microenvironment after radiation-induced damages. These effects of hUCBDSCs are more potent than those of hBMSCs. In conclusion, our findings suggest the role of hUCBDSCs to facilitate hematopoietic reconstitution and engraftment when cotransplanted with hematopoietic cells.

摘要

我们之前的研究表明,人脐带血基质细胞(hUCBDSCs)支持造血干细胞的生长,并比人骨髓基质细胞(hBMSCs)更有效地促进巨核细胞集落形成单位(CFU-Mk)的扩增。鉴于 hUCBDSCs 在体外巨核细胞生成中的独特作用,在这项后续研究中,我们进一步研究了它们在造血干细胞(HSC)移植背景下对体内造血的影响。在将造血细胞单独或与 hUCBDSCs 或 hBMSCs 一起输注到致死性照射的 BABL/c 小鼠后,我们通过流式细胞术检查了人 CD45+细胞在小鼠骨髓中的植入情况,观察了照射小鼠的存活率,在移植后不同时间点获得了血液计数和骨髓活检,并评估了造血细胞的集落形成和归巢效率。通过比较有或没有基质细胞的 HSC 移植,我们在这里表明 hUCBDSCs 有效地促进了造血细胞向骨髓的归巢,并增强了共移植后的植入。它们还促进了造血重建,特别是巨核细胞系的重建,并恢复了辐射诱导损伤后受损的基质微环境。hUCBDSCs 的这些作用比 hBMSCs 更强。总之,我们的发现表明 hUCBDSCs 在与造血细胞共移植时有助于促进造血重建和植入。

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