Ayyadurai V A Shiva, Deonikar Prabhakar, Radhakrishnan Vishvatha, Keating Armand
Systems Biology Group, CytoSolve Research Division, CytoSolve, Inc., Cambridge, MA 02138, United States.
Open Science Institute, International Center for Integrative Systems, Cambridge, MA 02138, United States.
Stem Cells. 2025 Aug 22;43(9). doi: 10.1093/stmcls/sxaf042.
A systems-level understanding of immunomodulatory, regenerative, and pro-/antifibrosis functions of mesenchymal stromal cells (MSCs) is critical to advance MSCs as a viable therapeutic option. Given the complexity of MSCs and their interactions with microenvironmental cells, a systems biology approach may enable such understanding to achieve practical objectives such as target identification, combination therapeutics, clinical strategies, and avoidance of adverse effects. In this study, a molecular systems architecture of MSCs microenvironment is developed to organize the complexity of biomolecular interactions between MSCs and other microenvironmental cells. This architecture provides a visual mapping of MSC interactions, identifies the complex crosstalk between MSCs and cells in the microenvironment, reveals potential targets, and offers a framework for creating future predictive, quantitative computational (in silico) models of the MSC microenvironment. The development of combination therapeutics, clinical strategies to improve therapeutic efficacy, and avoidance of adverse effects can be facilitated by such in silico models. However, it must all begin with a molecular systems architecture of MSCs-the objective and result of this study.
从系统层面理解间充质基质细胞（MSC）的免疫调节、再生及促/抗纤维化功能，对于将MSC发展成为一种可行的治疗选择至关重要。鉴于MSC及其与微环境细胞相互作用的复杂性，系统生物学方法可能有助于实现诸如靶点识别、联合治疗、临床策略制定以及避免不良反应等实际目标。在本研究中，构建了MSC微环境的分子系统架构，以梳理MSC与其他微环境细胞之间生物分子相互作用的复杂性。该架构提供了MSC相互作用的可视化图谱，识别了MSC与微环境中细胞之间的复杂串扰，揭示了潜在靶点，并为创建未来预测性、定量计算（计算机模拟）的MSC微环境模型提供了框架。此类计算机模拟模型有助于联合治疗的开发、提高治疗效果的临床策略制定以及避免不良反应。然而，这一切都必须始于MSC的分子系统架构——本研究的目标和成果。
