...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Connexin 43 as a signaling platform for increasing the volume and spatial distribution of regenerated tissue
【24h】

Connexin 43 as a signaling platform for increasing the volume and spatial distribution of regenerated tissue

机译:连接蛋白43作为增加再生组织体积和空间分布的信号平台

获取原文
获取原文并翻译 | 示例
           

摘要

Gap junction intercellular communication (GJIC) is ubiquitous in the majority of vertebrate cells and is required for the proper development of most tissues. The loss of gap junction-mediated cell-to-cell communication leads to compromised development in many tissues and organs. Because cells constantly interact through gap junctions to coordinate tissue functions and homeostasis, we hypothesized that increasing cell-to-cell communication, via genetically engineering cells to overexpress gap junction proteins, could enhance cell differentiation in the interior regions of 3D tissue equivalents, thereby increasing the ability to regenerate larger and more uniform volumes of tissue. To test this hypothesis, we used bone as a model tissue because of the difficulty in achieving spatially uniform bone regeneration in 3D. In bone marrow stromal cells (BMSC), GJIC and osteogenic differentiation were compromised in 3D cultures relative to 2D monolayers and in the core of 3D cultures relative to the surface. Overexpression of connexin 43 (Cx43) via transduction of BMSCs with a lentivirus overcame this problem, enhancing both the magnitude and spatial distribution of GJIC and osteogenic differentiation markers throughout 3D constructs. Transplantation of cells overexpressing Cx43 resulted in an increased volume fraction and spatial uniformity of bone in vivo, relative to nontransduced BMSCs. Increased GJIC also enhanced the effect of a potent osteoinductive agent (BMP-7), suggesting a synergism between the soluble factor and GJIC. These findings present a platform to improve cell-to-cell communication in 3D and to achieve uniformly distributed tissue regeneration in 3D.
机译:间隙连接细胞间通讯(GJIC)在大多数脊椎动物细胞中普遍存在,并且是大多数组织正常发育所必需的。间隙连接介导的细胞间通讯的丧失导致许多组织和器官的发育受损。由于细胞不断通过间隙连接相互作用来协调组织功能和体内平衡,因此我们推测,通过基因工程改造细胞以过表达间隙连接蛋白来增强细胞间通信可以增强3D组织等同物内部区域的细胞分化,从而增加再生更大,更均匀体积的组织的能力。为了验证这一假设,我们使用骨骼作为模型组织,因为难以在3D模式下实现空间均匀的骨骼再生。在骨髓基质细胞(BMSC)中,相对于2D单层,在3D培养物中和在相对于表面的3D培养核心中,GJIC和成骨分化受到损害。通过慢病毒转导BMSC来过度表达连接蛋白43(Cx43)克服了这个问题,在整个3D构建体中增强了GJIC和成骨分化标志物的大小和空间分布。相对于未转导的BMSC,过表达Cx43的细胞移植导致体内骨骼的体积分数和空间均匀性增加。 GJIC的增加还增强了强效骨诱导剂(BMP-7)的作用,表明可溶性因子和GJIC之间存在协同作用。这些发现提供了一个平台,可改善3D中的细胞间通信并实现3D中均匀分布的组织再生。

著录项

  • 来源
  • 作者单位

    Departments of Biomedical Engineering, University of Michigan, Ann Arbor, Ml, 48109-1078;

    Departments of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Ml, 48109-1078;

    Department of Cardiology, Johns Hopkins University, Baltimore, MD;

    Departments of Biomedical Engineering, University of Michigan, Ann Arbor, Ml, 48109-1078 Departments of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Ml, 48109-1078;

    Departments of Biomedical Engineering, University of Michigan, Ann Arbor, Ml, 48109-1078 Departments of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Ml, 48109-1078;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    bone regeneration; cell-cell communication; gap junctions; virus;

    机译:骨再生;单元间通信;缝隙连接;病毒;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号