Delivery of Immobilized IFN-γ With PCN-333 and Its Effect on Human Mesenchymal Stem Cells
Delivery of Immobilized IFN-γ With PCN-333 and Its Effect on Human Mesenchymal Stem Cells
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PCN-333 固定化 IFN-γ 的递送及其对人间充质干细胞的影响
DOI：
10.1021/acsbiomaterials.2c01038
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发表时间：
2023
影响因子：
5.8
通讯作者：
Almodovar, Jorge
中科院分区：
文献类型：
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作者：
Phipps, Josh;Haseli, Mahsa;Pinzon-Herrera, Luis;Wilson, Ben;Corbitt, Joshua;Servoss, Shannon;Almodovar, Jorge
干扰素-γ（IFN-γ）在调节用于细胞疗法的人间充质干/基质细胞（hMSC）的免疫抑制特性中起着至关重要的作用。然而，IFN-γ的生物利用度低，在培养基中降解，在hMSC的生产过程中使用IFN-γ时产生了挑战。金属-有机框架（MOFs）具有多孔内部、生物相容性、高负载能力和被功能化用于靶向的能力，已经成为越来越合适的蛋白质递送平台。在这项工作中，我们合成了MOF PCN-333（Fe），并表明它可以用于将IFN-γ递送到hMSCs的局部细胞外环境。在这样做的过程中，细胞适当地增殖和分化，没有观察到副作用。我们证明了含有IFN-γ的PCN-333（Fe）MOFs对hMSC没有细胞毒性，可以促进在免疫应答中起作用的蛋白质的表达，并且能够在较低浓度下诱导类似于可溶性IFN-γ的吲哚胺2，3-双加氧酶（IDO）的产生。总的来说，使用M0 F递送IFN-γ可以在未来用于制造治疗相关的hMSC。
Interferon-gamma (IFN-γ) plays a vital role in modulating the immunosuppressive properties of human mesenchymal stem/stromal cells (hMSCs) used in cell therapies. However, IFN-γ suffers from low bioavailability and degrades in media, creating a challenge when using IFN-γ during the manufacturing of hMSCs. Metal–organic frameworks (MOFs), with their porous interiors, biocompatibility, high loading capacity, and ability to be functionalized for targeting, have become an increasingly suitable platform for protein delivery. In this work, we synthesize the MOF PCN-333(Fe) and show that it can be utilized to immobilize and deliver IFN-γ to the local extracellular environment of hMSCs. In doing so, the cells proliferate and differentiate appropriately with no observed side effects. We demonstrate that PCN-333(Fe) MOFs containing IFN-γ are not cytotoxic to hMSCs, can promote the expression of proteins that play a role in immune response, and are capable of inducing indoleamine 2,3-dioxygenase (IDO) production similar to that of soluble IFN-γ at lower concentrations. Overall, using MOFs to deliver IFN-γ may be leveraged in the future in the manufacturing of therapeutically relevant hMSCs.