Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into the NOD/SCID mouse and their role in supporting human CD34 cell engraftment

Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into the NOD/SCID mouse and their role in supporting human CD34 cell engraftment
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DOI:
10.1182/blood-2003-04-1121
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发表时间:
2004-05-01
期刊:
影响因子:
20.3
通讯作者:
Lopez, M
Lopez, M
中科院分区:
医学1区
文献类型:
--
作者:
Bensidhoum, M;Chapel, A;Lopez, M

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Stro-1抗原可能定义间充质干细胞(MSC)祖细胞亚群。我们在此报道了体外扩增的Stro-1(+)或Stro-1(-)MSC亚群在非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠模型中对人CD 34(+)脐带血细胞移植的作用。数据显示,与单独输注CD 34(+)细胞相比,扩增的Stro-1-细胞与CD 34+细胞共移植导致血液或骨髓(BM)和脾脏中检测到的人CD 45、CD 34、CD 19和CD 11b细胞显著增加。向小鼠输注扩增的Stro-1(+)和Stro-1(-)细胞(无CD 34(+)细胞)显示Stro-1(+)-衍生的细胞数量(如通过用定量聚合酶链反应[PCR]对人β-珠蛋白进行DNA分析所评估的)在脾、肌肉、BM和肾中高于Stro-1(-)衍生的细胞,而在肺中发现更多的Stro-1(-)-来源的细胞比Stro-1(+)-来源的细胞。用增强型绿色荧光蛋白(eGFP)基因转导扩增的Stro-1(+)细胞并不改变它们的细胞因子释放和它们在NOD/ SCID小鼠组织中的归巢。扩增的Stro-1(+)和Stro-1(-)细胞的造血支持和归巢能力之间的差异对于临床治疗应用可能是重要的:Stro-1(+)细胞可能更适合用于组织中的基因递送,而Stro-1(-)细胞可能更适合用于支持造血移植。(C)2004年,美国血液学会。
The Stro-1 antigen potentially defines a mesenchymal stem cell (MSC) progenitor subset. We here report on the role of human ex vivo-expanded selected Stro-1(+) or Stro-1(-) MSC subsets on the engraftment of human CD34(+) cord blood cells in the nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse model. The data show that cotransplantation of expanded Stro-1- cells with CD34+ cells resulted in a significant increase of human CD45, CD34, CD19, and CD11b cells detected in blood or in bone marrow (BM) and spleen as compared with the infusion of CD34(+) cells alone. Infusion into mice of expanded Stro-1(+) and Stro-1(-) cells (without CD34(+) cells) showed that the numbers of Stro-1(+) -derived (as assessed by DNA analysis of human beta-globin with quantitative polymerase chain reaction [PCR]) were higher than Stro-1(-)-derived cells in spleen, muscles, BM, and kidneys, while more Stro-1(-)-derived than Stro-1(+)-derived cells were found in lungs. The transduction of expanded Stro-1(+) cells with an enhanced green fluorescent protein (eGFP) gene did not modify their cytokine release and their homing in NOD/ SCID mouse tissues. The difference between the hematopoietic support and the homing capabilities of expanded Stro-1(+) and Stro-1(-) cells may be of importance for clinical therapeutic applications: Stro-1(+) cells may rather be used for gene delivery in tissues while Stro-1(-) cells may rather be used to support hematopoietic engraftment. (C) 2004 by The American Society of Hematology.