Université Paris Cité, CNRS, INSERM, B3OA, Paris, France.
École Nationale Vétérinaire d'Alfort, B3OA, Maisons-Alfort, France.
Tissue Eng Part B Rev. 2023 Feb;29(1):47-61. doi: 10.1089/ten.TEB.2022.0063. Epub 2023 Jan 25.
Mesenchymal stromal cells (MSCs) are considered promising candidates for regenerative medicine applications. Their clinical performance postimplantation, however, has been disappointing. This lack of therapeutic efficacy is most likely due to suboptimal formulations of MSC-containing material constructs. Tissue engineers, therefore, have developed strategies addressing/incorporating optimized cell, microenvironmental, biochemical, and biophysical cues/stimuli to enhance MSC-containing construct performance. Such approaches have had limited success because they overlooked that maintenance of MSC viability after implantation for a sufficient time is necessary for MSCs to develop their regenerative functionalities fully. Following a brief overview of glucose metabolism and regulation in MSCs, the present literature review includes recent pertinent findings that challenge old paradigms and notions. We hereby report that glucose is the primary energy substrate for MSCs, provides precursors for biomass generation, and regulates MSC functions, including proliferation and immunosuppressive properties. More importantly, glucose metabolism is central in controlling MSC expansion, MSC viability, and MSC-mediated angiogenesis postimplantation when addressing MSC-based therapies. Meanwhile, models are highlighted for predicting the glucose needs of MSCs in specific regenerative medicine settings, which will eventually enable tissue engineers to design viable and potent tissue constructs. This new knowledge should be incorporated into developing novel effective MSC-based therapies. Impact statement The clinical use of mesenchymal stromal cells (MSCs) has been unsatisfactory due to the inability of MSCs to survive and be functional after implantation for sufficient periods to mediate directly or indirectly a successful regenerative tissue response. The present review summarizes the endeavors in the past, but, most importantly, reports the latest findings that elucidate underlying mechanisms and identify glucose metabolism as the crucial parameter in MSC survival and the subsequent functions pertinent to new tissue formation of importance in tissue regeneration applications. These latest findings justify further basic research and the impetus for developing new strategies to improve the modalities and efficacy of MSC-based therapies.
间充质基质细胞（MSCs）被认为是再生医学应用中很有前途的候选者。然而，它们在植入后的临床性能一直令人失望。这种治疗效果不佳很可能是由于 MSC 含量材料构建体的配方不理想。因此，组织工程师已经开发了一些策略来解决/纳入优化的细胞、微环境、生化和生物物理线索/刺激物，以提高含有 MSC 的构建体的性能。这些方法的成功有限，因为它们忽略了 MSC 在植入后有足够的时间维持活力对于 MSC 充分发挥其再生功能是必要的。在简要概述 MSCs 中的葡萄糖代谢和调节后，本文献综述包括最近的相关发现，这些发现挑战了旧的模式和概念。我们在此报告葡萄糖是 MSCs 的主要能量底物，为生物量生成提供前体，并调节 MSC 的功能，包括增殖和免疫抑制特性。更重要的是，当涉及基于 MSC 的治疗时，葡萄糖代谢是控制 MSC 扩增、MSC 活力和 MSC 介导的植入后血管生成的核心。同时，还突出了模型，以预测特定再生医学环境中 MSC 的葡萄糖需求，这最终将使组织工程师能够设计可行且有效的组织构建体。新知识应纳入开发新的有效的基于 MSC 的治疗方法。
影响说明 由于 MSCs 在植入后无法存活并发挥功能足够长的时间来直接或间接介导成功的再生组织反应，因此 MSCs 的临床应用一直不尽如人意。本综述总结了过去的努力，但最重要的是报告了最新的发现，这些发现阐明了潜在的机制，并确定了葡萄糖代谢是 MSC 存活及其随后与新组织形成相关的功能的关键参数，这对于组织再生应用中重要的新组织形成至关重要。这些最新发现证明了进一步进行基础研究和开发新策略来改善基于 MSC 的治疗方式和效果的合理性。
