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人骨髓来源的多能间充质干细胞在小鼠子宫内的移植

In utero transplantation of human bone marrow-derived multipotent mesenchymal stem cells in mice.

作者信息

Chou Shiu-Huey, Kuo Tom K, Liu Ming, Lee Oscar K

机构信息

Department of Life Science, Fu-Jen University, 510 Zhongzheng Road, Hsinehuang City, Taipei 242, Taiwan, Republic of China.

出版信息

J Orthop Res. 2006 Mar;24(3):301-12. doi: 10.1002/jor.20047.

DOI:10.1002/jor.20047
PMID:16482576
Abstract

Mesenchymal stem cells (MSCs) are multipotent cells that can be isolated from human bone marrow and possess the potential to differentiate into progenies of embryonic mesoderm. However, current evidence is based predominantly on in vitro experiments. We used a murine model of in utero transplantation (IUT) to study the engraftment capabilities of human MSCs. MSCs were obtained from bone marrow by negative immunoselection and limiting dilution, and were characterized by flow cytometry and by in vitro differentiation into osteoblasts, chondrocytes, and adipocytes. MSCs were transplanted into fetal mice at a gestational age of 14 days. Engraftment of human MSCs was determined by flow cytometry, polymerase chain reaction, and fluorescence in situ hybridization (FISH). MSCs engrafted into tissues originating from all three germ layers and persisted for up to 4 months or more after delivery, as evidenced by the expression of the human-specific beta-2 microglobulin gene and by FISH for donor-derived cells. Donor-derived CD45+ cells were detectable in the peripheral blood of recipients, suggesting the participation of MSCs in hematopoiesis at the fetal stage. This model can further serve to evaluate possible applications of MSCs.

摘要

间充质干细胞(MSCs)是多能细胞,可从人骨髓中分离得到,并具有分化为胚胎中胚层后代细胞的潜力。然而,目前的证据主要基于体外实验。我们使用了一种子宫内移植(IUT)的小鼠模型来研究人MSCs的植入能力。通过阴性免疫筛选和有限稀释从骨髓中获取MSCs,并通过流式细胞术以及体外分化为成骨细胞、软骨细胞和脂肪细胞对其进行表征。在妊娠14天时将MSCs移植到胎鼠体内。通过流式细胞术、聚合酶链反应和荧光原位杂交(FISH)来确定人MSCs的植入情况。人特异性β-2微球蛋白基因的表达以及对供体来源细胞的FISH检测证明,MSCs植入到了源自所有三个胚层的组织中,并在出生后持续存在长达4个月或更长时间。在受体的外周血中可检测到供体来源的CD45+细胞,这表明MSCs在胎儿阶段参与了造血过程。该模型可进一步用于评估MSCs的潜在应用。

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引用本文的文献

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Cell Transplant. 2018 Jan;27(1):130-139. doi: 10.1177/0963689717728937.
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Rapidly self-renewing human multipotent marrow stromal cells (hMSC) express sialyl Lewis X and actively adhere to arterial endothelium in a chick embryo model system.快速自我更新的人类多能骨髓基质细胞(hMSC)表达唾液酸化路易斯X,并在鸡胚模型系统中积极黏附于动脉内皮。
PLoS One. 2014 Aug 21;9(8):e105411. doi: 10.1371/journal.pone.0105411. eCollection 2014.
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Benefits of hypoxic culture on bone marrow multipotent stromal cells.
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Am J Blood Res. 2012;2(3):148-59. Epub 2012 Oct 20.
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Intravenous injection of mesenchymal stem cells is effective in treating liver fibrosis.静脉注射间充质干细胞对治疗肝纤维化有效。
World J Gastroenterol. 2012 Mar 14;18(10):1048-58. doi: 10.3748/wjg.v18.i10.1048.
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