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评估海藻酸钠微球在固体器官间充质干细胞移植中的作用。

Evaluation of alginate microspheres for mesenchymal stem cell engraftment on solid organ.

机构信息

INSERM U858, CHU Rangueil, Toulouse Cedex 4, France.

出版信息

Cell Transplant. 2010;19(12):1623-33. doi: 10.3727/096368910X514297. Epub 2010 Aug 17.

Abstract

Mesenchymal stem cells (MSCs) may be used as a cell source for cell therapy of solid organs due to their differentiation potential and paracrine effect. Nevertheless, optimization of MSC-based therapy needs to develop alternative strategies to improve cell administration and efficiency. One option is the use of alginate microencapsulation, which presents an excellent biocompatibility and an in vivo stability. As MSCs are hypoimmunogenic, it was conceivable to produce microparticles with [alginate-poly-L-lysine-alginate (APA) microcapsules] or without (alginate microspheres) a surrounding protective membrane. Therefore, the aim of this study was to determine the most suitable microparticles to encapsulate MSCs for engraftment on solid organ. First, we compared the two types of microparticles with 4 × 10(6) MSCs/ml of alginate. Results showed that each microparticle has distinct morphology and mechanical resistance but both remained stable over time. However, as MSCs exhibited a better viability in microspheres than in microcapsules, the study was pursued with microspheres. We demonstrated that viable MSCs were still able to produce the paracrine factor bFGF and did not present any chondrogenic or osteogenic differentiation, processes sometimes reported with the use of polymers. We then proved that microspheres could be implanted under the renal capsule without degradation with time or inducing impairment of renal function. In conclusion, these microspheres behave as an implantable scaffold whose biological and functional properties could be adapted to fit with clinical applications.

摘要

间充质干细胞(MSCs)可作为实体器官细胞治疗的细胞来源,因为它们具有分化潜能和旁分泌作用。然而,基于 MSC 的治疗的优化需要开发替代策略来提高细胞给药和效率。一种选择是使用藻酸盐微胶囊化,其具有优异的生物相容性和体内稳定性。由于 MSCs 免疫原性低,因此可以生产具有[藻酸盐-聚-L-赖氨酸-藻酸盐(APA)微胶囊]或无(藻酸盐微球)周围保护膜的微球。因此,本研究的目的是确定最适合包封 MSC 以用于实体器官植入的微球。首先,我们比较了两种类型的微球与 4×106/ml 藻酸盐的 MSC。结果表明,每种微球都具有独特的形态和机械强度,但都能长时间保持稳定。然而,由于 MSC 在微球中的活力优于微胶囊中的活力,因此研究继续使用微球进行。我们证明,存活的 MSC 仍能够产生旁分泌因子 bFGF,并且不会发生软骨形成或成骨分化,这些过程有时会在使用聚合物时发生。然后我们证明微球可以在不随时间降解或不损害肾功能的情况下植入肾包膜下。总之,这些微球作为一种可植入的支架,其生物学和功能特性可以适应临床应用。

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