Bone marrow is a reservoir of repopulating mesangial cells during glomerular remodeling
Bone marrow is a reservoir of repopulating mesangial cells during glomerular remodeling
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DOI：
10.1681/asn.v12122625
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发表时间：
2001-12-01
影响因子：
13.6
通讯作者：
Hori, M
中科院分区：
文献类型：
--
作者：
Ito, T;Suzuki, A;Hori, M
肾小球，其细胞成分是从间充质发育而来的，在过滤血浆中起着关键作用。肾小球成分的不可逆转的变化是肾功能损害的开始和进展的原因。最近，已经表明功能性干细胞存在于成人身体的骨髓中，并且它们可以重建间充质来源的受损组织。为了检查骨髓是否为受损的肾小球提供干细胞，以系统性和组成性方式建立了携带增强型绿色荧光蛋白（EGFP大鼠）的转基因大鼠。在将EGFP大鼠的骨髓移植到野生型大鼠中后，用EGFP标签追踪移植的骨髓细胞的后代。在抗Thy 1抗体介导的肾小球肾炎中，系膜溶解引起的骨髓源性细胞向肾小球的募集显著促进。在恢复的肾小球中，11%至12%的肾小球细胞来自移植的骨髓。骨髓来源的CD 45（+）细胞数量在疾病过程中短暂增加，并且CD 45阴性细胞始终占肾小球中骨髓来源细胞群的一半以上。骨髓来源的Thy 1（+）细胞数量不断增加，直到重塑停止，最终占肾小球细胞的7%至8%。激光扫描显微镜显示骨髓来源的Thy 1（+）细胞为肾小球毛细血管提供结构支持，表明它们是系膜细胞。尽管CD 45（-）Thy 1（-）骨髓源性细胞在肾小球重塑过程中存在，但只要检测它们，它们都不表达内皮标志物，如因子VIII和RECA 1。结果表明，骨髓可在体内产生系膜细胞。
The renal glomerulus, whose cellular components are developmentally derived from the mesenchyme, plays a pivotal role in filtratating plasma. Irretrievable changes of glomerular components are responsible for the initiation and progression of impaired renal function. Recently, it has been shown that functional stem cells exist in the bone marrow of adult bodies and that they can reconstitute damaged tissues of the mesenchymal origin. To examine whether the bone marrow provides stem cells to damaged glomeruli, transgenic rats carrying enhanced green fluorescence protein (EGFP rat) were established in a systemic and constitutive manner. After transplanting the bone marrow of EGFP rats into wild-type rats, the progeny of the transplanted marrow cells were tracked with a tag of EGFP. Recruitment of bone marrow-derived cells into glomeruli was dramatically facilitated in response to mesangiolysis evoked in anti-Thy1 antibody-mediated glomerulonephritis. In the restored glomeruli, 11% to 12% of glomerular cells were derived from the transplanted bone marrow. The number of bone marrow-derived CD45(+) cells transiently increased during the disease process, and CD45-negative cells constantly accounted for more than half of the bone marrow-derived population in glomeruli. Bone marrow-derived Thy1(+) cells kept increasing in number until the remodeling ceased and finally made up 7% to 8% of glomerular cells. Laser scanning microscopy displayed that the bone marrow-derived Thy1(+) cells provide structural support for glomerular capillaries, which indicates that they are mesangial cells. Although CD45(-)Thy1(-) bone marrow-derived cells exist during the remodeling of glomeruli, none of them expressed endothelial markers such as Factor VIII and RECA1 as long as they were tested. The results indicate that the bone marrow can give rise to mesangial cells in vivo.