Takada Eiichiro, Mizuno Hayato L, Takeoka Yoshiki, Mizuno Shuichi
Department of Orthopedic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
Front Bioeng Biotechnol. 2024 Sep 6;12:1440434. doi: 10.3389/fbioe.2024.1440434. eCollection 2024.
3D multicellular self-organized cluster models, e.g., organoids are promising tools for developing new therapeutic modalities including gene and cell therapies, pharmacological mechanistic and screening assays. Various applications of these models have been used extensively for decades, however, the mechanisms of cluster formation, maintenance, and degradation of these models are not even known over in-vitro-life-time. To explore such advantageous models mimicking native tissues or organs, it is necessary to understand aforementioned mechanisms. Herein, we intend to clarify the mechanisms of the formation of cell clusters. We previously demonstrated that primary chondrocytes isolated from distinct longitudinal depth zones in articular cartilage formed zone-specific spherical multicellular clusters . To elucidate the mechanisms of such cluster formation, we simulated it using the computational Cellular Potts Model with parameters were translated from gene expression levels and histological characteristics corresponding to interactions between cell and extracellular matrix. This simulation was validated morphologically with cluster formation and . Since zone specific chondrocyte cluster models showed similarity with corresponding model, the has a potential to be used for prediction of the 3D multicellular models used for development, disease, and therapeutic models.
3D多细胞自组织簇模型，例如类器官，是开发包括基因和细胞疗法、药理机制和筛选试验在内的新治疗方法的有前途的工具。这些模型的各种应用已经广泛使用了几十年，然而，在体外生命周期内，这些模型的簇形成、维持和降解机制甚至还不清楚。为了探索这种模仿天然组织或器官的优势模型，有必要了解上述机制。在此，我们旨在阐明细胞簇形成的机制。我们之前证明，从关节软骨不同纵向深度区域分离的原代软骨细胞形成了区域特异性球形多细胞簇。为了阐明这种簇形成的机制，我们使用计算细胞Potts模型进行模拟，其参数从基因表达水平和与细胞和细胞外基质之间相互作用相对应的组织学特征转换而来。该模拟通过簇形成在形态上得到了验证。由于区域特异性软骨细胞簇模型与相应模型显示出相似性，因此它有可能用于预测用于发育、疾病和治疗模型的3D多细胞模型。
