Analysis of chemotactic molecules in bone marrow-derived mesenchymal stem cells and the skin: Ccl27-Ccr10 axis as a basis for targeting to cutaneous tissues.
Analysis of chemotactic molecules in bone marrow-derived mesenchymal stem cells and the skin: Ccl27-Ccr10 axis as a basis for targeting to cutaneous tissues.
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DOI：
10.1016/j.jcyt.2012.11.006
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发表时间：
2013-02
期刊：
影响因子：
4.5
通讯作者：
Igoucheva, Olga
中科院分区：
文献类型：
--
作者：
Alexeev, Vitali;Donahue, Adele;Uitto, Jouni;Igoucheva, Olga
关键词：
成体干细胞产生大量的细胞外基质（ECM）分子，具有作为皮肤结缔组织疾病的细胞疗法的巨大潜力。然而，基于干细胞的方法的主要挑战与全身输注干细胞到皮肤的低效归巢有关。我们通过对间充质干细胞 (MSC) 中的趋化分子进行全面的表达分析，以及正常和遗传性大疱性表皮松解症 (EB) 影响皮肤的特定皮肤组织，研究了控制间充质干细胞 (MSC) 定向迁移到皮肤的趋化机制。对短期和长期 MSC 培养物中趋化因子受体的分析表明，几种受体的组织培养依赖性表达。对表皮和真皮来源的趋化因子的评估表明，大多数皮肤来源的趋化信号优先招募不同组的白细胞而不是 MSC。对来自受 EB 影响的非起泡皮肤的趋化分子的分析表明，所选趋化因子和受体的表达仅发生微小变化。尽管如此，这些数据使我们能够将 Ccl27-Ccr10 趋化轴定义为最有效地将 MSC 募集到皮肤的趋化轴。我们的体内分析表明，MSC 上 Ccr10 的均匀表达和皮肤中 Ccl27 水平的改变增强了干细胞从循环中的外渗，并促进它们在皮肤组织内的迁移。总的来说，我们的研究对正常和受 EB 影响的皮肤中的趋化信号进行了全面分析，并提供了概念验证数据，证明趋化途径的改变可以增强治疗性干细胞的皮肤归巢。
The adult stem cells produce a plethora of extracellular matrix (ECM) molecules and have a high potential as cell-based therapeutics for connective tissue disorders of the skin. However, the primary challenge of the stem cell-based approach is associated with the inefficient homing of systemically infused stem cells to the skin. We examined chemotactic mechanisms that govern directional migration of the mesenchymal stem cells (MSCs) into the skin by conducting a comprehensive expression analysis of chemotactic molecules in MSCs and defined cutaneous tissues from normal and hereditary epidermolysis bullosa (EB)-affected skin. Analysis of chemokine receptors in short and long-term MSC cultures showed tissue culture-dependent expression of several receptors. Assessment of epidermis- and dermis-derived chemokines showed that majority of skin-originated chemotactic signals preferentially recruit different sets of leukocytes rather than MSCs. Analysis of the chemotactic molecules derived from EB-affected non-blistered skin showed only minor changes in expression of selected chemokines and receptors. Nevertheless, the data allowed us to define Ccl27-Ccr10 chemotactic axis as the most potent for the recruitment of MSCs to the skin. Our in vivo analysis demonstrated that uniform expression of Ccr10 on MSCs and alteration of Ccl27 level in the skin enhance extravasation of stem cells from circulation and facilitate their migration within cutaneous tissue. Collectively, our study provides a comprehensive analysis of chemotactic signal in normal and EB-affected skin and proof-of-concept data demonstrating that alteration of the chemotactic pathways can enhance skin homing of the therapeutic stem cells.
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DOI：
10.1016/j.biocel.2008.07.011
发表时间：
2009-03-01
影响因子：
4
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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