Reconstitution of Schwannian stroma in neuroblastomas using human bone marrow stromal cells
Reconstitution of Schwannian stroma in neuroblastomas using human bone marrow stromal cells
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DOI：
10.2353/ajpath.2008.070309
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发表时间：
2008-10-01
影响因子：
6
通讯作者：
Yamada, Taketo
中科院分区：
文献类型：
--
作者：
Du, Wenlin;Hozumi, Nobumichi;Yamada, Taketo
神经母细胞瘤中的雪旺氏间质与患者预后有关。关于神经母细胞瘤中许旺间质的起源存在争议：一种理论认为许旺细胞来源于肿瘤细胞，另一种理论认为它们来自神经母细胞瘤周围的正常细胞。我们研究了人骨髓基质细胞（hBMSCs）或人间充质干细胞（hMSCs）能否在神经母细胞瘤中分化为雪旺细胞。将hBMSCs或hMSCs与增强型绿色荧光蛋白（EGFP）沿着注射到具有严重联合免疫缺陷的非肥胖糖尿病小鼠的异种移植神经母细胞瘤中，并使用免疫组织化学分析所得肿瘤。将HBMSCs和hMSCs与神经母细胞瘤细胞共培养，并监测雪旺细胞特异性分子S100 β和Egr-2的诱导。S100 β阳性的雪旺氏间质仅在含有mBMSCs或hMSCs的神经母细胞瘤中观察到，但在神经母细胞瘤中未观察到。缺少这些细胞。用抗S100和抗EGFP抗体双重染色显示，神经母细胞瘤中S100阳性细胞也呈EGFP阳性。相比之下，hBMSCs在尤文氏肉瘤中没有发育成雪旺细胞，表明移植的hBMSCs或hMSCs分化成雪旺细胞特异性地发生在神经母细胞瘤中。S100 β和Egr-2在hBMSCs或与神经母细胞瘤细胞共培养的hMSCs中均有表达。HBMSCs或hMSCs可能有助于人类肿瘤间质的形成。施旺氏基质。的神经母细胞瘤似乎是来自非肿瘤基质细胞，而不是神经母细胞瘤细胞，进一步阐明其发展的起源。
The Schwannian stroma in neuroblastomas is related to patient prognosis. There is debate surrounding the origin of Schwannian stroma in neuroblastomas: one theory is that the Schwann cells are derived from neoplastic cells, and the other is that they arise from normal cells surrounding the neuroblastoma. We examined whether human bone marrow stromal cells (hBMSCs) or human mesenchymal stem cells (hMSCs) could differentiate into Schwann cells in neuroblastomas. hBMSCs or hMSCs along with enhanced green fluorescent protein (EGFP) were injected into xeno-transplanted neuroblastomas in nonobese diabetic mice with severe combined immunodeficiency and the resulting tumors were analyzed using immunohistochemistry. HBMSCs and hMSCs were co-cultured with neuroblastoma cells, and the induction of Schwann cell-specific molecules, S100beta and Egr-2, was monitored. S100beta-positive Schwannian stroma was observed only in neuroblastomas containing either mBMSCs or hMSCs, but not in neuroblastomas. lacking these cells. Double staining with anti-S100 and anti-EGFP antibodies showed that S100-positive cells in neuroblastomas were also EGFP-positive. By contrast, hBMSCs did not develop into Schwann cells in Ewing's sarcoma, demonstrating that differentiation of transplanted hBMSCs or hMSCs into Schwann cells occurs specifically in neuroblastomas. Both S100beta and Egr-2 were expressed in hBMSCs or hMSCs co-cultured with neuroblastoma cells. HBMSCs or hMSCs may contribute to the formation of human tumor stroma. The Schwannian stroma. of neuroblastomas appears to be derived from nonneoplastic stromal cells rather than neuroblastoma cells, further clarifying its developmental origins.