Engineering degradable, 'tuneable' microcarriers for the bulk culture of therapeutically active mesenchymal stem cell

使用间充质干细胞(MSCs)进行基于细胞的治疗是一种令人兴奋的治疗选择，它使用我们自己的细胞来抑制炎症和促进受损组织的修复。有效的治疗应用需要大量的骨髓间充质干细胞，需要在实验室中进行扩增。这可能会导致它们由于自发分化而失去重要的免疫调节和修复功能。该项目将以现有知识为基础，制造新的微载体，这种载体可以优化以提供黏附信号和可调的弹性，为骨髓间充质干细胞提供最佳的生长表面条件。此外，该项目还研究了MSCs在反应器中释放的关键可溶性因子，如含有生物活性分子的胞外小泡。已知这些因子具有免疫调节特性，当与MSCs结合时，可以提供一种双重治疗方法。这种“可调”的新微载体系统将包含缓释晶体，允许直接输送生长因子，而不是调节MSC功能。重要的是，这些载体将是可降解的，允许轻松收集扩大的细胞用于进一步测试。这使得MSCs能够高效、标准化和可扩展地扩展，用于治疗或科学研究。

Cell based therapies using Mesenchymal Stromal Cells (MSCs) are an exciting therapeutic option, using our own cells to both dampen inflammation and promote repair of damaged tissues. Large numbers of MSCs are required for effective therapeutic applications, requiring expansion in the laboratory. This can result in loss of their important immuno-modulatory and repair functions due to spontaneous differentiation.This project will build on current knowledge to manufacture new microcarriers which can be optimized to provide both adhesive signals, and 'tuneable' elasticity to provide MSCs with the optimal growth surface conditions. Additionally, this project investigates key soluble factors released by MSCs in the reactor, such as extracellular vesicles containing bioactive molecules. Such factors are known to possess immunomodulatory properties and can provide a dual approach to therapy when combined with MSCs.This 'tuneable' new microcarrier system will incorporate slow-release crystals allowing direct delivery of growth factors than can modulate MSC function. Importantly, these carriers will be degradable, allowing for easy collection of expanded cells for further testing. This allows for efficient, standardised, and scalable expansion of MSCs for use in therapy or scientific research.