IGF-1-mediated osteoblastic niche expansion enhances long-term hematopoietic stem cell engraftment after murine bone marrow transplantation
IGF-1-mediated osteoblastic niche expansion enhances long-term hematopoietic stem cell engraftment after murine bone marrow transplantation
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DOI：
10.1002/stem.1463
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发表时间：
2013-10-01
期刊：
影响因子：
5.2
通讯作者：
Horwitz, Edwin M.
中科院分区：
文献类型：
--
作者：
Caselli, Anna;Olson, Timothy S.;Horwitz, Edwin M.
骨髓移植后造血干细胞（HSC）植入的效率在很大程度上取决于骨髓微环境接受移植细胞的能力。虽然骨髓的放射性消融损伤成骨干细胞龛，但对其恢复和调控其对植入移植的HSC的接受性的机制知之甚少。我们先前报道了骨髓放射性消融后骨髓骨内膜微环境的快速恢复和显著扩张。在这里，我们表明，这种重组代表了成熟的骨内膜成骨细胞的增殖，这似乎是从一个小的子集的高增殖性，相对耐辐射的骨内膜细胞。全身照射后48小时内，骨内膜表面沿着形成多层成骨细胞，同时骨髓细胞因子表达达到峰值。这种生态位重组促进移植的造血细胞归巢到宿主骨髓空间和长期HSC的植入。抑制胰岛素样生长因子（IGF）-1-受体酪氨酸激酶信号传导消除骨内膜成骨细胞增殖和供体HSC植入，表明细胞因子IGF-1是骨内膜龛重组和供体HSC植入的关键介质。进一步了解IGF-1依赖性成骨细胞龛扩张和HSC植入的新机制可能会产生临床应用，以提高临床HSC移植后的植入效率。干细胞2013;31：2193-2204
The efficiency of hematopoietic stem cell (HSC) engraftment after bone marrow (BM) transplantation depends largely on the capacity of the marrow microenvironment to accept the transplanted cells. While radioablation of BM damages osteoblastic stem cell niches, little is known about their restoration and mechanisms governing their receptivity to engraft transplanted HSCs. We previously reported rapid restoration and profound expansion of the marrow endosteal microenvironment in response to marrow radioablation. Here, we show that this reorganization represents proliferation of mature endosteal osteoblasts which seem to arise from a small subset of high-proliferative, relatively radio-resistant endosteal cells. Multiple layers of osteoblasts form along the endosteal surface within 48 hours after total body irradiation, concomitant with a peak in marrow cytokine expression. This niche reorganization fosters homing of the transplanted hematopoietic cells to the host marrow space and engraftment of long-term-HSC. Inhibition of insulin-like growth factor (IGF)-1-receptor tyrosine kinase signaling abrogates endosteal osteoblast proliferation and donor HSC engraftment, suggesting that the cytokine IGF-1 is a crucial mediator of endosteal niche reorganization and consequently donor HSC engraftment. Further understanding of this novel mechanism of IGF-1-dependent osteoblastic niche expansion and HSC engraftment may yield clinical applications for improving engraftment efficiency after clinical HSC transplantation. Stem Cells 2013;31:2193-2204