Contribution of bone marrow hematopoietic stem cells to adult mouse inner ear: Mesenchymal cells and fibrocytes
Contribution of bone marrow hematopoietic stem cells to adult mouse inner ear: Mesenchymal cells and fibrocytes
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DOI：
10.1002/cne.20929
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发表时间：
2006-05-10
影响因子：
2.5
通讯作者：
Schulte, BA
中科院分区：
文献类型：
--
作者：
Lang, HN;Ebihara, Y;Schulte, BA
骨髓（BM）来源的干细胞显示出可塑性，具有分化成各种特化细胞的能力。为了验证内耳的一些细胞来源于骨髓的假设，我们将分离的整个骨髓细胞或克隆扩增的表达增强绿色荧光蛋白（EGFP）的转基因小鼠制备的造血干细胞（hsc）移植到辐照的成年小鼠中。分离的GFP(+) BM细胞也被移植到注射了busulfan的孕鼠衍生的条件新生小鼠中（busulfan可以消融新生儿的造血干细胞）。移植后3-20个月定量GFP（+）细胞。在所有移植条件下，内耳均可见GFP（+）细胞。它们在螺旋韧带内最丰富，但在其他通常由纤维细胞和间充质细胞占据的位置也发现。移植小鼠内耳未见GFP（+）神经元和毛细胞。双免疫荧光分析显示，大多数GFP（+）细胞对CD45（巨噬细胞和造血细胞标志物）呈阴性。螺旋韧带中的一部分GFP（+）细胞表达免疫反应性Na、k - atp酶或Na- k - cl转运蛋白（NKCC），这些蛋白被用作特化离子转运纤维细胞的标记物。表型研究表明，GFP（+）细胞不是由供体细胞与内源细胞融合产生的。本研究首次证实内耳细胞来源于骨髓，更确切地说是来源于造血干细胞。结果表明，包括成人内耳纤维细胞在内的间充质细胞可以连续地从造血干细胞中获得。
Bone marrow (BM)-derived stem cells have shown plasticity with a capacity to differentiate into a variety of specialized cells. To test the hypothesis that some cells in the inner ear are derived from BM, we transplanted either isolated whole BM cells or clonally expanded hematopoietic stem cells (HSCs) prepared from transgenic mice expressing enhanced green fluorescent protein (EGFP) into irradiated adult mice. Isolated GFP(+) BM cells were also transplanted into conditioned newborn mice derived from pregnant mice injected with busulfan (which ablates HSCs in the newborns). Quantification of GFP(+) cells was performed 3-20 months after transplant. GFP(+) cells were found in the inner ear with all transplant conditions. They were most abundant within the spiral ligament but were also found in other locations normally occupied by fibrocytes and mesenchymal cells. No GFP(+) neurons or hair cells were observed in inner ears of transplanted mice. Dual immunofluorescence assays demonstrated that most of the GFP(+) cells were negative for CD45, a macrophage and hematopoietic cell marker. A portion of the GFP(+) cells in the spiral ligament expressed immunoreactive Na, K-ATPase, or the Na-K-Cl transporter (NKCC), proteins used as markers for specialized ion transport fibrocytes. Phenotypic studies indicated that the GFP(+) cells did not arise from fusion of donor cells with endogenous cells. This study provides the first evidence for the origin of inner ear cells from BM and more specifically from HSCs. The results suggest that mesenchymal cells, including fibrocytes in the adult inner ear, may be derived continuously from HSCs.