Formation of hematopoietic territories and bone by transplanted human bone marrow stromal cells requires a critical cell density
Formation of hematopoietic territories and bone by transplanted human bone marrow stromal cells requires a critical cell density
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DOI：
10.1016/j.exphem.2007.01.051
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发表时间：
2007-06-01
影响因子：
2.6
通讯作者：
Robey, Pamela Gehron
中科院分区：
文献类型：
--
作者：
Mankani, Mahesh H.;Kuznetsov, Sergei A.;Robey, Pamela Gehron
Objective.骨髓基质细胞（BMSC）包括具有在体内移植后形成成熟骨器官的能力的多能细胞。这些骨器官中的造血作用归因于骨骼干细胞的作用，骨骼干细胞能够向骨和造血支持基质分化。然而，造血区域的产生可能部分是形成足够成熟和大的骨微环境的自然结果。在这里，我们首次描述了BMSC数量与异位移植中骨/造血形成程度之间的关系。将人骨髓基质细胞与羟基磷灰石/磷酸三钙一起沿着移植到免疫耐受小鼠体内，采用一系列剂量;移植后随访长达29个月。骨和造血形成的程度随着BMSC数量的增加而增加;然而，这种关系是S形的，并且BMCs的阈值数量对于广泛的骨形成或任何造血都是必要的。造血仅发生在广泛骨形成的同时，骨形成差的地方没有造血发生。与我们早期长期BMSC移植的研究一致，移植物在8周后发生了骨形态学的变化，但骨含量没有变化。我们的研究结果提供了证据表明，造血和成熟骨器官的形成是足够高的局部密度的骨髓基质细胞的结果，因为它是骨骼干细胞作用的产物。(c)2007年国际实验血液学学会。爱思唯尔公司出版
Objective. Bone marrow stromal cells (BMSCs) include multipotent cells with the ability to form mature bone organs upon in vivo transplantation. Hematopoiesis in these bone organs has been ascribed to the action of skeletal stem cells, which are capable of differentiating towards bone and hematopoiesis-supporting stroma. Yet, the creation of hematopoietic territories may be in part a natural consequence of the formation of a sufficiently mature and large bone microenvironment. Here, we describe, for the first time, a relationship between BMSC numbers and the extent of bone/hemtopoiesis formation in heterotopic transplants.Methods. Human BMCs were transplanted along with hydroxyapatite/tricalcium phosphate, utilizing a spectrum of dosages, into immunotolerant mice; the transplants were followed for up to 29 months.Results. The extent of bone and hematopoiesis formation increased with increasing BMSC numbers; however, the relationship was sigmoid in character, and a threshold number of BMCs was necessary for extensive bone formation or any hematopoiesis. Hematopoiesis only occurred in conjunction with extensive bone formation, and no hematopoiesis occurred where bone formation was poor. Consistent with our earlier studies of long-term BMSC transplantation, the transplants underwent a change in bone morphology but not bone content after 8 weeks.Conclusion. Our results have provided evidence that the formation of both hematopoiesis and a mature bone organ is as much a consequence of a sufficiently high local density of bone marrow stromal cells as it is the product of skeletal stem cell action. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc.