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首页> 外文学位 >Regulation of bone marrow mesenchymal stem cells, cell-cell, and cell-matrix interactions.
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Regulation of bone marrow mesenchymal stem cells, cell-cell, and cell-matrix interactions.

机译：骨髓间充质干细胞，细胞间和细胞间相互作用的调节。

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Bone marrow mesenchymal stem cells (MSCs) represent one of the most important adult stem cell types for regenerative medicine. These cells provide a reliable cell source for tissue engineering and cell-based therapies. Although MSCs have been isolated from many tissues in addition to bone marrow, their regulation in highly specialized physiological microenvironments is still largely unclear. This thesis addressed this issue from three important aspects using well-defined in vitro models and attempted to utilize the information obtained from these model systems for tissue engineering applications.; First, this thesis addressed the regulation of MSCs by the neighboring cells in their physiological microenvironment using a well-defined MSC-osteoblast coculture system, as osteoblasts coexist with MSCs in bone in close proximity. Osteoblasts have been found to regulate bone marrow hematopoietic stem cells, but their role in MSC regulation is unclear. This thesis discovered that osteoblasts regulate MSCs through WNT and cadherin pathways and the regulation mechanism depends on cell-cell contact modes (direct vs. indirect).; The second aspect of MSC regulation addressed in this thesis is the interaction between MSCs and extracellular matrix in a 2D environment. This was realized by a model system, in which a vitamin-C functionalized polymer was used to create a highly specific matrix for MSCs. The results showed that the vitamin-C functionalized polymer matrix regulates MSCs attachment, spreading, proliferation, and differentiation. More importantly, this functionalized polymer was capable of preserving the differentiation capacity of the MSCs, a phenomenon related to cellular aging.; The third part of this thesis focuses on the regulation of MSCs in 3D environments, created by an engineered porous silk scaffold with highly connected pore structures. Silk as the strongest naturally occurring polymer material has gained increasing interest in biomedical applications, as reviewed extensively in this thesis. The 3D porous silk scaffold provides a suitable environment for MSCs to differentiate into chondrocytes in serum free medium supplemented by dexamethasone and transforming growth factor-beta. It was also found that MSC (i.e. stem cell) based cartilage tissue engineering has fundamental differences from chondrocyte (i.e. primary cell) based cartilage tissue engineering.; In summary, this thesis addressed three essential aspects of the regulation of MSCs and the findings have important implications in MSC biology and MSC-based cellular therapy.
机译：骨髓间充质干细胞（MSC）代表了再生医学最重要的成人干细胞类型之一。这些细胞为组织工程和基于细胞的疗法提供了可靠的细胞来源。尽管已经从骨髓中从许多组织中分离出了MSC，但是它们在高度专门化的生理微环境中的调控仍不清楚。本文从三个重要方面出发，使用定义明确的体外模型解决了这一问题，并试图将从这些模型系统中获得的信息用于组织工程应用。首先，由于成骨细胞与骨髓间充质干细胞共存于骨中，成骨细胞与骨髓间充质干细胞共存，从而解决了MSCs在生理微环境中由相邻细胞对MSCs的调控问题。已经发现成骨细胞可调节骨髓造血干细胞，但它们在MSC调节中的作用尚不清楚。本论文发现成骨细胞通过WNT和钙黏着蛋白途径调控MSCs，其调控机制取决于细胞与细胞的接触方式（直接与间接）。本文研究的MSC调控的第二个方面是在二维环境中MSC与细胞外基质之间的相互作用。这是通过模型系统实现的，在模型系统中，使用了维生素C功能化的聚合物为MSC创建了高度特异性的基质。结果表明，维生素C功能化的聚合物基质调节MSCs的附着，扩散，增殖和分化。更重要的是，这种功能化的聚合物能够保留MSC的分化能力，这是一种与细胞衰老有关的现象。本文的第三部分着重于在3D环境中对MSC的调控，这是由具有高度连接的孔结构的工程化多孔丝支架产生的。丝绸作为最强的天然存在的高分子材料，在生物医学应用中已引起越来越多的关注，正如本论文中广泛论述的那样。 3D多孔丝支架为MSC提供了一个合适的环境，使其在不含地塞米松和转化生长因子-β的无血清培养基中分化为软骨细胞。还发现基于MSC（即干细胞）的软骨组织工程与基于软骨细胞（即原代细胞）的软骨组织工程具有根本的区别。综上所述，本论文探讨了MSC调控的三个基本方面，这些发现对MSC生物学和基于MSC的细胞治疗具有重要意义。

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