Hached Fahd, Vinatier Claire, Pinta Pierre-Gabriel, Hulin Philippe, Le Visage Catherine, Weiss Pierre, Guicheux Jérôme, Billon-Chabaud Aurélie, Grimandi Gaël
INSERM, UMR 1229, Regenerative Medicine and Skeleton (RMeS), Université de Nantes, ONIRIS, 44042 Nantes, France.
UFR Sciences Biologiques et Pharmaceutiques, Université de Nantes, 44035 Nantes, France.
Stem Cells Int. 2017;2017:9303598. doi: 10.1155/2017/9303598. Epub 2017 Oct 11.
While therapeutically interesting, the injection of MSCs suffers major limitations including cell death upon injection and a massive leakage outside the injection site. We proposed to entrap MSCs within spherical particles derived from alginate, as a control, or from silanized hydroxypropyl methylcellulose (Si-HPMC). We developed water in an oil dispersion method to produce small Si-HPMC particles with an average size of about 68 m. We evidenced a faster diffusion of fluorescein isothiocyanate-dextran in Si-HPMC particles than in alginate ones. Human adipose-derived MSCs (hASC) were encapsulated either in alginate or in Si-HPMC, and the cellularized particles were cultured for up to 1 month. Both alginate and Si-HPMC particles supported cell survival, and the average number of encapsulated hASC per alginate and Si-HPMC particle (7102 and 5100, resp.) did not significantly change. The stimulation of encapsulated hASC with proinflammatory cytokines resulted in the production of IDO, PGE, and HGF whose concentration was always higher when cells were encapsulated in Si-HPMC particles than in alginate ones. We have demonstrated that Si-HPMC and alginate particles support hASC viability and the maintenance of their ability to secrete therapeutic factors.
虽然具有治疗意义,但注射间充质干细胞存在重大局限性,包括注射时细胞死亡以及大量泄漏到注射部位以外。我们提议将间充质干细胞包裹在由藻酸盐(作为对照)或硅烷化羟丙基甲基纤维素(Si-HPMC)制成的球形颗粒中。我们开发了油包水分散法来制备平均尺寸约为68μm的小Si-HPMC颗粒。我们证明了异硫氰酸荧光素-葡聚糖在Si-HPMC颗粒中的扩散比在藻酸盐颗粒中更快。人脂肪来源的间充质干细胞(hASC)被包裹在藻酸盐或Si-HPMC中,并且将细胞化颗粒培养长达1个月。藻酸盐和Si-HPMC颗粒都支持细胞存活,并且每个藻酸盐和Si-HPMC颗粒中包裹的hASC的平均数量(分别为7×10²和5×10⁰)没有显著变化。用促炎细胞因子刺激包裹的hASC会导致吲哚胺2,3-双加氧酶(IDO)、前列腺素E(PGE)和肝细胞生长因子(HGF)的产生,当细胞被包裹在Si-HPMC颗粒中时,其浓度总是高于被包裹在藻酸盐颗粒中的情况。我们已经证明,Si-HPMC和藻酸盐颗粒支持hASC的活力及其分泌治疗因子能力的维持。