Centre for the Cellular Microenvironment, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, Mazumdar-Shaw Advanced Research Centre, University of Glasgow, Glasgow, G11 6EW, UK.
School of Biosciences, College of Health and Life Sciences, Aston University, Birmingham, B4 7ET, UK.
Nat Commun. 2023 Feb 10;14(1):753. doi: 10.1038/s41467-023-36293-7.
Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that are of considerable clinical potential in transplantation and anti-inflammatory therapies due to their capacity for tissue repair and immunomodulation. However, MSCs rapidly differentiate once in culture, making their large-scale expansion for use in immunomodulatory therapies challenging. Although the differentiation mechanisms of MSCs have been extensively investigated using materials, little is known about how materials can influence paracrine activities of MSCs. Here, we show that nanotopography can control the immunomodulatory capacity of MSCs through decreased intracellular tension and increasing oxidative glycolysis. We use nanotopography to identify bioactive metabolites that modulate intracellular tension, growth and immunomodulatory phenotype of MSCs in standard culture and during larger scale cell manufacture. Our findings demonstrate an effective route to support large-scale expansion of functional MSCs for therapeutic purposes.
间充质基质细胞（MSCs）是多能祖细胞，由于其组织修复和免疫调节能力，在移植和抗炎治疗中有很大的临床应用潜力。然而，MSCs 在培养中一旦分化，就会迅速分化，这使得大规模扩增以用于免疫调节治疗具有挑战性。尽管已经使用材料对 MSCs 的分化机制进行了广泛的研究，但对于材料如何影响 MSCs 的旁分泌活性却知之甚少。在这里，我们表明纳米形貌可以通过降低细胞内张力和增加氧化糖酵解来控制 MSCs 的免疫调节能力。我们使用纳米形貌来鉴定生物活性代谢物，这些代谢物可以调节标准培养和大规模细胞制造过程中 MSCs 的细胞内张力、生长和免疫调节表型。我们的研究结果表明了一种有效的途径，可以支持大规模扩增功能性 MSCs 以用于治疗目的。
