Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles.
Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles.
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DOI：
10.1016/j.bbrc.2015.12.061
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发表时间：
2016-01
影响因子：
3.1
通讯作者：
N. Sugino;Y. Miura;Hisayuki Yao;Masaki Iwasa;A. Fujishiro;Sumie Fujii;H. Hirai;A. Takaori-Kondo;T. Ichinohe;T. Maekawa
中科院分区：
文献类型：
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作者：
N. Sugino;Y. Miura;Hisayuki Yao;Masaki Iwasa;A. Fujishiro;Sumie Fujii;H. Hirai;A. Takaori-Kondo;T. Ichinohe;T. Maekawa
骨髓微环境在支持造血方面起着至关重要的作用。在这里，我们通过微阵列分析，证明了早期骨诱导阶段的人骨髓间充质基质/干细胞(e-MSCs)具有独特的造血相关基因表达，具有增强的造血支持能力。基因本体论和基因集浓缩分析表明，与未经骨诱导治疗的BM-MSCs相比，e-MSCs的细胞黏附和趋化相关基因表达发生了显著变化。值得注意的是，在e-MSCs中，造血相关分子CXCL12和血管细胞黏附分子1的表达显著减少。E-MSCs支持CD34+造血干/祖细胞的体外扩增和髓系细胞的生成。此外，短期的骨诱导治疗有利于接受骨髓移植的致死性照射小鼠的体内造血恢复。E-MSCs没有表现出干细胞相关基因表达的降低，成骨相关基因的表达增加，以及明显的矿化，从而保持了向成脂细胞分化的能力。我们的发现证明了e-MSCs作为骨髓间充质干细胞和骨祖细胞之间分化阶段的造血调控基质细胞的独特生物学特性，对于开发利用药物诱导成骨治疗支持造血干细胞和祖细胞移植的新策略具有重要意义。
Bone marrow (BM) microenvironment has a crucial role in supporting hematopoiesis. Here, by using a microarray analysis, we demonstrate that human BM mesenchymal stromal/stem cells (MSCs) in an early osteoinductive stage (e-MSCs) are characterized by unique hematopoiesis-associated gene expression with an enhanced hematopoiesis-supportive ability. In comparison to BM-MSCs without osteoinductive treatment, gene expression in e-MSCs was significantly altered in terms of their cell adhesion- and chemotaxis-related profiles, as identified with Gene Ontology and Gene Set Enrichment Analysis. Noteworthy, expression of the hematopoiesis-associated molecules CXCL12 and vascular cell adhesion molecule 1 was remarkably decreased in e-MSCs. e-MSCs supported an enhanced expansion of CD34+hematopoietic stem and progenitor cells, and generation of myeloid lineage cells in vitro. In addition, short-term osteoinductive treatment favored in vivo hematopoietic recovery in lethally irradiated mice that underwent BM transplantation. e-MSCs exhibited the absence of decreased stemness-associated gene expression, increased osteogenesis-associated gene expression, and apparent mineralization, thus maintaining the ability to differentiate into adipogenic cells. Our findings demonstrate the unique biological characteristics of e-MSCs as hematopoiesis-regulatory stromal cells at differentiation stage between MSCs and osteoprogenitor cells and have significant implications in developing new strategy for using pharmacological osteoinductive treatment to support hematopoiesis in hematopoietic stem and progenitor cell transplantation.