Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion
Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion
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DOI：
10.1016/s0301-472x(00)00635-4
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发表时间：
2001-02-01
影响因子：
2.6
通讯作者：
Hoffman, R
中科院分区：
文献类型：
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作者：
Devine, SM;Bartholomew, AM;Hoffman, R
Objective.人骨髓含有能够沿沿着多种间充质细胞谱系分化的间充质干细胞。使用非人灵长类动物模型，我们试图确定狒狒来源的间充质干细胞的全身输注是否与毒性相关，以及这些细胞是否能够归巢并持续存在于骨髓中。对五只狒狒（Papio anubis）进行致死性照射，然后静脉内自体造血祖细胞与已在培养物中扩增的自体（n = 3）或同种异体（n = 2）间充质干细胞组合。在这些狒狒中的四只中，间充质干细胞用编码增强型绿色荧光蛋白基因（n = 3）或人胎盘碱性磷酸酶基因（n = 1）的逆转录病毒载体进行遗传修饰，用于跟踪目的。第六只动物只接受静脉注射基因标记的自体间充质干细胞，但不接受造血干细胞或预处理照射。培养后，狒狒间充质干细胞在形态上表现为梭形细胞的同质群体，其通过单克隆抗体SH-3和SH-4鉴定。这些细胞不表达造血标志物CD 34或CD 45。从原代培养物中分离的狒狒间充质干细胞能够沿成脂和成骨谱系沿着。静脉输注间充质干细胞没有急性或慢性毒性。在所有五个基因标记的间充质干细胞的受体中，在移植后骨髓活检中检测到转基因。在接受自体间充质干细胞的两只动物中，包括一只非条件接受者，在输注后1年内可以检测到转基因。在一个异基因标记的骨髓间充质干细胞的受体中，在输注后76天在骨髓中检测到转基因。这些数据表明，狒狒间充质支架细胞：1）当静脉内施用时不与显著毒性相关，2）在静脉内输注后能够归巢至骨髓，和3）在全身施用后具有在骨髓内建立驻留持续时间延长的能力。(C)2001年国际实验血液学学会。出版社：Elsevier Science Inc.
Objective. The human bone marrow contains mesenchymal stem cells capable of differentiating along multiple mesenchymal cell lineages. Using a non-human primate model, we sought to determine whether the systemic infusion of baboon-derived mesenchymal stem cells was associated with toxicity and whether these cells were capable of homing to and persisting within the bone marrow.Materials and Methods. Five baboons (Papio anubis) were administered lethal irradiation followed by intravenous autologous hematopoietic progenitor cells combined with either autologous (n = 3) or allogeneic (n = 2) mesenchymal stem cells that had been expanded in culture. In four of these baboons, the mesenchymal stem cells were genetically modified with a retroviral vector encoding either the enhanced green fluorescent protein gene (n = 3) or the human placental alkaline phosphatase gene (n = 1) for tracking purposes. A sixth animal received only intravenous gene marked autologous mesenchymal stem cells but no hematopoietic stem cells or conditioning irradiation.Results. Following culture, baboon mesenchymal stem cells appeared morphologically as a homogeneous population of spindle-shaped cells that were identified by the monoclonal antibodies SH-3 and SH-4. These cells did not express the hematopoietic markers CD34 or CD45, Baboon mesenchymal stem cells isolated from primary culture were capable of differentiating along both adipogenic and osteogenic lineages. There was no acute or chronic toxicity associated with the intravenous infusion of mesenchymal stem cells. In all five recipients of gene marked mesenchymal stem cells, transgene was detected in post-transplant bone marrow biopsies. In two animals receiving autologous mesenchymal stem cells, including the one non-conditioned recipient, transgene could be detected over 1 year following infusion. In one recipient of allogeneic gene marked mesenchymal stem cells, transgene was detected in the hone marrow at 76 days following infusion.Conclusion. These data demonstrate that baboon mesenchymal stent cells: 1) are not associated with significant toxicity when administered intravenously, 2) are capable of homing to the bone marrow following intravenous infusion, and 3) have the capacity to establish residence within the bone marrow for an extended duration following systemic administration. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.