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[人脐带血间充质干细胞促进人脐带血来源的CD34+细胞在NOD/SCID小鼠体内的植入]

[Mesenchymal stem cells from human cord blood promote engraftment of human umbilical cord blood-derived CD34+ cells in NOD/SCID mice].

作者信息

Zhou Dun-hua, Huang Shao-liang, Huang Ke, Wu Yan-feng, Bao Rong, Wei Jing, Zhang Xu-chao, Li Yang

机构信息

Department of Pediatrics, Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510120, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2005 Dec;26(12):732-5.

PMID:16620577
Abstract

OBJECTIVE

To explore whether the co-transplantation of mesenchymal stem cells (MSC) from human umbilical cord blood (UCB) with UCB-derived CD34(+) cells in NOD/SCID mice could promote engraftment and accelerate hematopoiesis recovery.

METHODS

After sublethal irradiated ((60)Co 2.5 Gy), NOD/SCID mice received within 24 hours UCB CD34(+) cells (1 x 10(5) per mouse for low dosage group or 1 x 10(6) per mouse for high dosage group) with or without human UCB-derived MSC (1 x 10(6) per mouse) transplantation by lateral tail vein injection. Peripheral blood cells of transplanted mice were measured for white blood cell count, hemoglobin and platelet count at 10th, 20th, 30th, 40th and 56th day. At the end of 8th week after transplantation, all the alive mice were sacrificed and human derived CD45(+), CD45(+)CD3(+), CD45(+)CD19(+), CD45(+)CD33(+) cells in the bone marrow (BM) were assayed by flow cytometry.

RESULTS

(1) In the low dosage group, co-transplantation of MSC significantly raised the engraftment rate (26.02% vs 16.52%) (P < 0.05). (2) The survival rate in high dosage group was 80% for co-transplantation mice and 70% for CD34(+) cells alone transplantation mice. The survival rate in low dosage group was 70% for co-transplantation mice and 50% in CD34(+) cells transplantation mice. (3) In both dosages groups co-transplantation accelerated the hematopoiesis recovery. (4) At the end of 8 weeks after transplantation, in low dosage group, CD45(+)CD33(+) and CD45(+)CD19(+) cells were more in co-transplantation mice than in CD34(+) cells alone transplantation mice, but in high dosage group, the percentage of these two kinds of cells had no difference. In both dosage groups the percentage of CD45(+)CD41a(+) cells were higher in co-transplantation than in transplantation alone mice. CD45(+)CD3(+) cells were low in all groups.

CONCLUSIONS

(1) In low dosage transplantation, human UCB MSC could promote human CD34(+) cells engraftment in transplanted mice. (2) Co-transplantation of human UCB MSC and human UCB CD34(+) cells could significantly promote the hematopoiesis reconstitution and improve the survival rate of NOD/SCID mice. (3) MSC could promote human UCB CD34(+) cells to differentiated into B-lymphocytes, granulocyte and megakaryocyte in vivo.

摘要

目的

探讨人脐带血间充质干细胞(MSC)与脐带血来源的CD34(+)细胞共同移植到NOD/SCID小鼠体内是否能促进植入并加速造血恢复。

方法

对NOD/SCID小鼠进行亚致死剂量照射((60)Co 2.5 Gy)后,在24小时内通过尾静脉注射,将脐带血CD34(+)细胞(低剂量组每只小鼠1×10(5)个,高剂量组每只小鼠1×10(6)个)与或不与来源于人脐带血的MSC(每只小鼠1×10(6)个)进行移植。在移植后第10、20、30、40和56天测量移植小鼠外周血细胞的白细胞计数、血红蛋白和血小板计数。移植后第8周结束时,处死所有存活小鼠,通过流式细胞术检测骨髓中人类来源的CD45(+)、CD45(+)CD3(+)、CD45(+)CD19(+)、CD45(+)CD33(+)细胞。

结果

(1)在低剂量组中,MSC共同移植显著提高了植入率(26.02%对16.52%)(P < 0.05)。(2)高剂量组中,共同移植小鼠的存活率为80%,单独移植CD34(+)细胞的小鼠存活率为70%。低剂量组中,共同移植小鼠的存活率为70%,CD34(+)细胞移植小鼠的存活率为50%。(3)在两个剂量组中,共同移植均加速了造血恢复。(4)移植后第8周结束时,在低剂量组中,共同移植小鼠的CD45(+)CD33(+)和CD45(+)CD19(+)细胞比单独移植CD34(+)细胞的小鼠更多,但在高剂量组中,这两种细胞的百分比没有差异。在两个剂量组中,共同移植小鼠的CD45(+)CD41a(+)细胞百分比均高于单独移植小鼠。所有组中CD45(+)CD3(+)细胞均较低。

结论

(1)在低剂量移植中,人脐带血MSC可促进人CD34(+)细胞在移植小鼠体内的植入。(2)人脐带血MSC与人脐带血CD34(+)细胞共同移植可显著促进造血重建并提高NOD/SCID小鼠的存活率。(3)MSC可促进人脐带血CD34(+)细胞在体内分化为B淋巴细胞、粒细胞和巨核细胞。

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