Department of Clinical and Experimental Medicine, Linköping University, SE58185, Linköping, Sweden.
Biomater Sci. 2017 Oct 24;5(11):2241-2250. doi: 10.1039/c7bm00663b.
Human mesenchymal stromal cells (hMSCs) are adult-source cells that have been extensively evaluated for cell-based therapies. hMSCs delivered by intravascular injection have been reported to accumulate at the sites of injury to promote tissue repair and can also be employed as vectors for the delivery of therapeutic genes. However, the full potential of hMSCs remains limited as the cells are lost after injection due to anoikis and the adverse pathologic environment. Encapsulation of cells has been proposed as a means of increasing cell viability. However, controlling the release of therapeutic cells over time to target tissue still remains a challenge today. Here, we report the design and development of thermo-rheological responsive hydrogels that allow for precise, time dependent controlled-release of hMSCs. The encapsulated hMSCs retained good viability from 76% to 87% dependent upon the hydrogel compositions. We demonstrated the design of different blended hydrogel composites with modulated strength (S parameter) and looseness of hydrogel networks (N parameter) to control the release of hMSCs from thermo-responsive hydrogel capsules. We further showed the feasibility for controlled-release of encapsulated hMSCs within 3D matrix scaffolds. We reported for the first time by a systematic analysis that there is a direct correlation between the thermo-rheological properties associated with the degradation of the hydrogel composite and the cell release kinetics. This work therefore provides new insights into the further development of smart carrier systems for stem cell therapy.
人骨髓间充质干细胞（hMSCs）是一种成体来源的细胞，已被广泛评估用于细胞治疗。研究报道，通过血管内注射递送的 hMSCs 可以聚集在损伤部位，促进组织修复，也可以作为治疗基因递送的载体。然而，由于 hMSCs 在注射后会因失巢凋亡和不良病理环境而丢失，因此其全部潜力仍然受到限制。细胞包封已被提出作为提高细胞活力的一种手段。然而，控制治疗细胞随时间向目标组织的释放仍然是当今的一个挑战。在这里，我们报告了设计和开发热流变响应水凝胶的方法，该水凝胶可以精确地、随时间控制释放 hMSCs。根据水凝胶的组成，包封的 hMSCs 的存活率保持在 76%到 87%之间。我们展示了设计不同的混合水凝胶复合材料，通过调制强度（S 参数）和水凝胶网络的疏松度（N 参数）来控制 hMSCs 从热响应水凝胶胶囊中的释放。我们进一步展示了在 3D 基质支架内控制封装 hMSCs 释放的可行性。我们通过系统分析首次报道，与水凝胶复合材料降解相关的热流变特性与细胞释放动力学之间存在直接相关性。因此，这项工作为干细胞治疗的智能载体系统的进一步发展提供了新的见解。
