Collagen–Mesenchymal Stem Cell Microspheres Embedded in Hyaluronic Acid Solutions as Biphasic Stem Niche Delivery Systems for Pulmonary Differentiation,ACS Applied Bio Materials

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Collagen–Mesenchymal Stem Cell Microspheres Embedded in Hyaluronic Acid Solutions as Biphasic Stem Niche Delivery Systems for Pulmonary Differentiation
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2024-05-14 , DOI: 10.1021/acsabm.3c01218
Francesca Della Sala ₁ , Gennaro Longobardo _{1,

2} , Assunta Borzacchiello ₁

Affiliation

Cell therapy has the potential to become a feasible solution for several diseases, such as those related to the lungs and airways, considering the more beneficial intratracheal administration route. However, in lung diseases, an impaired pulmonary extracellular matrix (ECM) precludes injury resolution with a faulty engraftment of mesenchymal stem cells (MSCs) at the lung level. Furthermore, a shielding strategy to avoid cell damage as well as cell loss due to backflow through the injection path is required. Here, an approach to deliver cells encapsulated in a biomimetic stem niche is used, in which the interplay between cells and physiological lung ECM constituents, such as collagen and hyaluronic acid (HA), can occur. To this aim, a biphasic delivery system based on MSCs encapsulated in collagen microspheres (mCOLLs) without chemical modification and embedded in an injectable HA solution has been developed. Such biphasic delivery systems can both increase the mucoadhesive properties at the site of interest and improve cell viability and pulmonary differentiation. Rheological results showed a similar viscosity at high shear rates compared to the MSC suspension used in intratracheal administration. The size of the mCOLLs can be controlled, resulting in a lower value of 200 μm, suitable for delivery in alveolar sacs. Biological results showed that mCOLLs maintained good cell viability, and when they were suspended in lung medium implemented with low molecular weight HA, the differentiation ability of the MSCs was further enhanced compared to their differentiation ability in only lung medium. Overall, the results showed that this strategy has the potential to improve the delivery and viability of MSCs, along with their differentiation ability, in the pulmonary lineage.

中文翻译：

嵌入透明质酸溶液中的胶原蛋白-间充质干细胞微球作为肺分化的双相干细胞生态位递送系统

考虑到更有益的气管内给药途径，细胞疗法有可能成为多种疾病的可行解决方案，例如与肺和气道相关的疾病。然而，在肺部疾病中，肺细胞外基质（ECM）受损会妨碍肺水平间充质干细胞（MSC）错误植入的损伤消退。此外，还需要一种屏蔽策略来避免细胞损伤以及由于通过注射路径回流而导致的细胞损失。在这里，使用了一种递送封装在仿生干细胞生态位中的细胞的方法，其中细胞与生理肺 ECM 成分（如胶原蛋白和透明质酸（HA））之间的相互作用可以发生。为此，已经开发了一种基于封装在胶原蛋白微球（mCOLL）中的 MSC 的双相递送系统，无需化学修饰，并嵌入可注射的 HA 溶液中。这种双相递送系统既可以增加目标部位的粘膜粘附性，又可以提高细胞活力和肺分化。流变学结果显示，与气管内给药中使用的 MSC 混悬液相比，在高剪切速率下具有相似的粘度。mCOLL 的大小可以控制，从而产生 200 μm 的较低值，适合在肺泡囊中递送。生物学结果表明，mCOLL 保持了良好的细胞活力，当它们悬浮在低分子量 HA 实施的肺培养基中时，与仅在肺培养基中的分化能力相比，MSCs 的分化能力进一步增强。总体而言，结果表明，这种策略有可能改善 MSC 在肺系中的递送和活力，以及它们的分化能力。

更新日期：2024-05-14

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