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Application of a new cell-adhesive and cell-migatory molecule, laminin-5B, to regenerative medicine

新型细胞粘附和细胞迁移分子层粘连蛋白-5B在再生医学中的应用

基本信息

批准号：
17300157
负责人：
MIYAZAKI Kaoru
金额：
$ 8.96万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Laminins are a family of ECM proteins that are localized mainly in basement membranes and regulate various cellular functions such as adhesion, motility, proliferation, apoptosis and differentiation. More than 15 laminin isoforms consisting of different combinations of the three chains have been identified thus far. Among them, laminin-5 (α3A/B, β3, γ2 ; laminin-332), strongly promotes cellular adhesion and migration. Recently we established efficient expression systems of human recombinant laminin-5A (αA, β3, γ2) and laminin-5B (α3B, β3, γ2). In this study, we investigated the possibility to use these laminins for regenerative medicine. We also attempted to establish a system to produce a novel laminin isoform, laminin-6B (α3B, β1, γ1). Main results are as follows. 1) Mesenchymal stem cell (MSC) is thought to be an important cell type in the regenerative medicine, because it can differentiate into osteoblasts, chondrocytes, neural cells, muscle cells and some others. We found that laminin-5A and laminin-5B efficiently stimulated the growth of human MSCs in culture, while suppressing their chondrogenic differentiation. This suggest the possible use of laminin-5A/B as a growth-stimulatory supplement for the efficient in vitro growth of human MSCs. 2) The presence of laminin-6B is predicted, but it has never been identified. We found that this laminin existed in the basement membranes of micro-blood vessels in various human tissues. We also established an efficient expression system of this novel laminin by introducing cDNAs for human laminin α3B, β1, γ1 chains into HEK293 cells. (α3A, β3, γ2). This laminin may play an important role in angiogenesis and maintenance of vascular structures and functions.

层粘连蛋白（Laminins）是一个主要定位于基底膜的ECM蛋白家族，并调节多种细胞功能，如粘附、运动、增殖、凋亡和分化。到目前为止，已经鉴定出超过15种层粘连蛋白同工型，由这三条链的不同组合组成。其中，laminin-5 （α3A/B、β3、γ2; laminin-332）能强烈促进细胞粘附和迁移。近年来，我们建立了重组人laminin-5A （αA, β3, γ2）和laminin-5B （α3B, β3, γ2）的高效表达体系。在这项研究中，我们探讨了将这些层粘连蛋白用于再生医学的可能性。我们还试图建立一个系统，以产生新的层粘连蛋白异构体，层粘连蛋白6b （α3B, β1, γ1）。主要结果如下：1)间充质干细胞（Mesenchymal stem cell， MSC）可以分化为成骨细胞、软骨细胞、神经细胞、肌肉细胞等，被认为是再生医学中重要的细胞类型。我们发现laminin-5A和laminin-5B在培养中有效地刺激了人间充质干细胞的生长，同时抑制了它们的软骨分化。这表明可能使用层粘胶蛋白5a /B作为一种生长刺激补充剂，有效地促进人间充质干细胞的体外生长。2)预测了laminin-6B的存在，但从未被鉴定。我们发现这种层粘连蛋白存在于人体各种组织的微血管基底膜中。我们还通过将人层粘连蛋白α3B、β1、γ1链的cdna导入HEK293细胞，建立了该新型层粘连蛋白的高效表达体系。（α3a, β3, γ2）。这种层粘连蛋白可能在血管生成和维持血管结构和功能中起重要作用。