Carballo-Pedrares Natalia, Sanjurjo-Rodriguez Clara, Señarís Jose, Díaz-Prado Silvia, Rey-Rico Ana
Centro de Investigacións Científicas Avanzadas (CICA), Universidade da Coruña, As Carballeiras, s/n. Campus de Elviña, 15071 A Coruña, Spain.
Institute of Biomedical Research of A Coruña (INIBIC), University Hospital Complex A Coruña (CHUAC), Galician Health Service (SERGAS), 15006 A Coruña, Spain.
Pharmaceutics. 2022 Oct 28;14(11):2327. doi: 10.3390/pharmaceutics14112327.
Gene transfer to mesenchymal stem cells constitutes a powerful approach to promote their differentiation into the appropriate cartilage phenotype. Although viral vectors represent gold standard vehicles, because of their high efficiency, their use is precluded by important concerns including an elevated immunogenicity and the possibility of insertional mutagenesis. Therefore, the development of new and efficient non-viral vectors is under active investigation. In the present study, we developed new non-viral carriers based on niosomes to promote the effective chondrogenesis of human MSCs. Two different niosome formulations were prepared by varying their composition on non-ionic surfactant, polysorbate 80 solely (P80), or combined with poloxamer 407 (P80PX). The best niosome formulation was proven to transfer a plasmid, encoding for the potent chondrogenic transcription factor SOX9 in hMSC aggregate cultures. Transfection of hMSC aggregates via nioplexes resulted in an increased chondrogenic differentiation with reduced hypertrophy. These results highlight the potential of niosome formulations for gene therapy approaches focused on cartilage repair.
基因转移至间充质干细胞是促进其向合适软骨表型分化的有力方法。尽管病毒载体因其高效性而代表着金标准载体,但其使用因包括免疫原性升高和插入诱变可能性在内的重要问题而受到限制。因此,新型高效非病毒载体的研发正在积极进行中。在本研究中,我们基于脂质体开发了新型非病毒载体,以促进人骨髓间充质干细胞的有效软骨生成。通过改变其在非离子表面活性剂聚山梨酯80(仅P80)或与泊洛沙姆407组合(P80PX)上的组成,制备了两种不同的脂质体制剂。已证明最佳脂质体制剂可在人骨髓间充质干细胞聚集体培养物中转移编码强效软骨生成转录因子SOX9的质粒。通过脂质体复合物转染人骨髓间充质干细胞聚集体导致软骨生成分化增加且肥大减少。这些结果突出了脂质体制剂在专注于软骨修复的基因治疗方法中的潜力。