Sigmarsdottir Thora Bjorg, McGarrity Sarah, de Lomana Adrián López García, Kotronoulas Aristotelis, Sigurdsson Snaevar, Yurkovich James T, Rolfsson Ottar, Sigurjonsson Olafur Eysteinn
School of Science and Engineering, Reykjavík University, 101 Reykjavik, Iceland.
Center for Systems Biology, University of Iceland, 101 Reykjavik, Iceland.
Bioengineering (Basel). 2021 Dec 10;8(12):208. doi: 10.3390/bioengineering8120208.
Mesenchymal stromal cells (MSCs) are multipotent post-natal stem cells with applications in tissue engineering and regenerative medicine. MSCs can differentiate into osteoblasts, chondrocytes, or adipocytes, with functional differences in cells during osteogenesis accompanied by metabolic changes. The temporal dynamics of these metabolic shifts have not yet been fully characterized and are suspected to be important for therapeutic applications such as osteogenesis optimization. Here, our goal was to characterize the metabolic shifts that occur during osteogenesis. We profiled five key extracellular metabolites longitudinally (glucose, lactate, glutamine, glutamate, and ammonia) from MSCs from four donors to classify osteogenic differentiation into three metabolic stages, defined by changes in the uptake and secretion rates of the metabolites in cell culture media. We used a combination of untargeted metabolomic analysis, targeted analysis of C-glucose labelled intracellular data, and RNA-sequencing data to reconstruct a gene regulatory network and further characterize cellular metabolism. The metabolic stages identified in this proof-of-concept study provide a framework for more detailed investigations aimed at identifying biomarkers of osteogenic differentiation and small molecule interventions to optimize MSC differentiation for clinical applications.
间充质基质细胞（MSCs）是出生后的多能干细胞，在组织工程和再生医学中具有应用价值。MSCs可分化为成骨细胞、软骨细胞或脂肪细胞，在成骨过程中细胞具有功能差异，同时伴有代谢变化。这些代谢转变的时间动态尚未完全明确，并且被认为对于诸如优化成骨的治疗应用很重要。在此，我们的目标是描述成骨过程中发生的代谢转变。我们纵向分析了来自四名供体的MSCs的五种关键细胞外代谢物（葡萄糖、乳酸、谷氨酰胺、谷氨酸和氨），以便根据细胞培养基中代谢物摄取和分泌速率的变化将成骨分化分为三个代谢阶段。我们结合了非靶向代谢组学分析、对C-葡萄糖标记的细胞内数据的靶向分析以及RNA测序数据，以重建基因调控网络并进一步描述细胞代谢。在这项概念验证研究中确定的代谢阶段为更详细的研究提供了一个框架，这些研究旨在识别成骨分化的生物标志物以及小分子干预措施，以优化MSCs分化用于临床应用。
