Mesenchymal stem-cell (MSC)-based therapies have been recognized as promising strategies for the treatment of various injuries or diseases because of their unique characteristics, such as self-renewal, differentiation potential, and secretion of various bioactive molecules. However, MSC transplantation often results in low efficacy, including a cell viability loss and a low therapeutic activity. Alternatively, MSC spheroids have been studied to improve the viability and therapeutic activity of MSCs. Also, microencapsulation of cells can protect and retain the cells from harsh environments after transplantation. Here, MSC spheroids were formed in hyaluronic acid/alginate (HA@Alg) core–shell microcapsules and employed for neovascularization. A well-defined core–shell structure of HA@Alg microcapsules was produced by optimizing various electrospraying conditions. MSC spheroids could be spontaneously formed in the HA core of the microcapsules after 1 day of incubation. Enhanced secretion of various growth factors was found from MSC spheroids in HA@Alg. In vivo plug assay revealed the significant promotion of angiogenesis by MSC spheroids in HA@Alg compared to that by the controls (i.e., MSCs and MSC spheroids), which is likely because of the better retention of MSC spheroid forms in the microcapsules. Thus, the HA@Alg microcapsules embedding MSC spheroids will be greatly beneficial for various stem cell-based therapies.

中文翻译：

---

透明质酸/藻酸盐核-壳微胶囊中促血管生成间充质干细胞球体的原位形成。

基于间充质干细胞（MSC）的疗法因其独特的特性（例如自我更新，分化潜能和各种生物活性分子的分泌）而被认为是治疗各种损伤或疾病的有前途的策略。但是，MSC移植通常导致功效低下，包括细胞活力丧失和低治疗活性。备选地，已经研究了MSC球体以改善MSC的生存力和治疗活性。同样，细胞的微囊化可以在移植后保护细胞并使其免受恶劣环境的影响。在这里，MSC球状体由透明质酸/藻酸盐（HA @ Alg）核壳微胶囊形成，并用于新血管形成。通过优化各种电喷雾条件，可以生产出定义明确的HA @ Alg微胶囊核-壳结构。孵育1天后，MSC球体可在微胶囊的HA核心中自发形成。发现HA @ Alg中的MSC球体增加了各种生长因子的分泌。体内栓塞试验显示，与对照（即MSCs和MSC球状体）相比，MSC球状体在HA @ Alg中显着促进了血管生成，这可能是因为MSC球状体在微囊中保留得更好。因此，嵌入MSC球体的HA @ Alg微胶囊将对各种基于干细胞的疗法非常有益。