Chen Michael J, Whiteley Jonathan P, Please Colin P, Ehlicke Franziska, Waters Sarah L, Byrne Helen M
School of Mathematical Sciences, The University of Adelaide, Adelaide, SA, Australia.
Mathematical Institute, University of Oxford, Oxford, UK.
J Tissue Eng. 2019 Apr 22;10:2041731419842431. doi: 10.1177/2041731419842431. eCollection 2019 Jan-Dec.
A key step in the tissue engineering of articular cartilage is the chondrogenic differentiation of mesenchymal stem cells (MSCs) into chondrocytes (native cartilage cells). Chondrogenesis is regulated by transforming growth factor- (TGF-), a short-lived cytokine whose effect is prolonged by storage in the extracellular matrix. Tissue engineering applications aim to maximise the yield of differentiated MSCs. Recent experiments involve seeding a hydrogel construct with a layer of MSCs lying below a layer of chondrocytes, stimulating the seeded cells in the construct from above with exogenous TGF- and then culturing it in vitro. To investigate the efficacy of this strategy, we develop a mathematical model to describe the interactions between MSCs, chondrocytes and TGF-. Using this model, we investigate the effect of varying the initial concentration of TGF-, the initial densities of the MSCs and chondrocytes, and the relative depths of the two layers on the long-time composition of the tissue construct.
关节软骨组织工程的一个关键步骤是间充质干细胞（MSC）向软骨细胞（天然软骨细胞）的软骨形成分化。软骨形成受转化生长因子-（TGF-）调节，TGF-是一种半衰期短的细胞因子，其作用通过储存在细胞外基质中得以延长。组织工程应用旨在使分化的间充质干细胞产量最大化。最近的实验包括在水凝胶构建体中接种一层位于软骨细胞层下方的间充质干细胞，从上方用外源性TGF-刺激构建体中的接种细胞，然后在体外进行培养。为了研究该策略的有效性，我们建立了一个数学模型来描述间充质干细胞、软骨细胞和TGF-之间的相互作用。利用这个模型，我们研究了改变TGF-的初始浓度、间充质干细胞和软骨细胞的初始密度以及两层的相对深度对组织构建体长期组成的影响。
