CD13 promotes mesenchymal stem cell-mediated regeneration of ischemic muscle.
CD13 promotes mesenchymal stem cell-mediated regeneration of ischemic muscle.
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DOI：
10.3389/fphys.2013.00402
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发表时间：
2014
影响因子：
4
通讯作者：
Shapiro LH
中科院分区：
文献类型：
--
作者：
Rahman MM;Subramani J;Ghosh M;Denninger JK;Takeda K;Fong GH;Carlson ME;Shapiro LH
间充质干细胞(MSCs)是一种多能的组织驻留细胞，可以促进组织再生，因此显示出巨大的潜在治疗药物的前景。功能性MSCs已从多种成体组织中分离和鉴定，并通过一组核心MSCs标记物的共同表达而被普遍识别。这些标记物之一是多功能细胞表面肽酶CD13，它已被证明在人和小鼠的许多组织的MSCs上表达。为了研究CD13的普遍表达是否表明CD13在MSC生物学中的功能作用，我们从野生型(WT)和CD13KO小鼠的骨髓中分离、扩增和鉴定了MSCs。对这些细胞的鉴定表明，WT和CD13KO MSCs都表达完整的MSC标志物(CD29、CD44、CD49e、CD105、Sca1)，具有相似的增殖率，并能够向成脂和成骨方向分化。然而，缺乏CD13的MSCs不能分化为血管细胞，这与我们之前对CD13作为血管生成调节因子的特征一致。与WT MSCs相比，CD13KO MSCs在各种细胞外基质上的黏附和迁移明显受损，这与磷酸化FAK水平降低和细胞骨架改变有关。用活化的CD13抗体交联人MSCs可增加细胞与内皮单分子层的黏附，并以时间依赖的方式诱导FAK激活。与这些体外实验数据相一致的是，肌肉注射CD13KO MSCs的肢体严重缺血损伤模型与接受WT MSCs的模型相比，其血流灌注率显著降低，行走能力减少，坏死增加，血管形成受损。本研究提示CD13调节FAK的激活，促进MSC的黏附和迁移，从而有助于MSC介导的组织修复。CD13可能为提高间充质干细胞治疗的疗效提供了一个可行的靶点。
Mesenchymal stem cells (MSCs) are multipotent, tissue-resident cells that can facilitate tissue regeneration and thus, show great promise as potential therapeutic agents. Functional MSCs have been isolated and characterized from a wide array of adult tissues and are universally identified by the shared expression of a core panel of MSCs markers. One of these markers is the multifunctional cell surface peptidase CD13 that has been shown to be expressed on human and murine MSCs from many tissues. To investigate whether this universal expression indicates a functional role for CD13 in MSC biology we isolated, expanded and characterized MSCs from bone marrow of wild type (WT) and CD13KO mice. Characterization of these cells demonstrated that both WT and CD13KO MSCs expressed the full complement of MSC markers (CD29, CD44, CD49e, CD105, Sca1), showed comparable proliferation rates and were capable of differentiating toward the adipogenic and osteogenic lineages. However, MSCs lacking CD13 were unable to differentiate into vascular cells, consistent with our previous characterization of CD13 as an angiogenic regulator. Compared to WT MSCs, adhesion and migration on various extracellular matrices of CD13KO MSCs were significantly impaired, which correlated with decreased phospho-FAK levels and cytoskeletal alterations. Crosslinking human MSCs with activating CD13 antibodies increased cell adhesion to endothelial monolayers and induced FAK activation in a time dependent manner. In agreement with these in vitro data, intramuscular injection of CD13KO MSCs in a model of severe ischemic limb injury resulted in significantly poorer perfusion, decreased ambulation, increased necrosis and impaired vascularization compared to those receiving WT MSCs. This study suggests that CD13 regulates FAK activation to promote MSC adhesion and migration, thus, contributing to MSC-mediated tissue repair. CD13 may present a viable target to enhance the efficacy of mesenchymal stem cell therapies.
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DOI：
10.1016/0005-2744(80)90202-8
发表时间：
1980-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
MCCLELLAN, JB;GARNER, CW
通讯作者：
GARNER, CW
影响因子：
5.5
作者：
Hu, Xinyang;Wei, Ling;Yu, Shan Ping
通讯作者：
Yu, Shan Ping
影响因子：
13.6
作者：
Mina-Osorio P
通讯作者：
Mina-Osorio P
影响因子：
3.7
作者：
Covas, DT;Piccinato, CE;Zago, MA
通讯作者：
Zago, MA
影响因子：
20.3
作者：
Bhagwat, SV;Petrovic, N;Shapiro, LH
通讯作者：
Shapiro, LH