Nebel Sabrina, Lux Manuel, Kuth Sonja, Bider Faina, Dietrich Wolf, Egger Dominik, Boccaccini Aldo R, Kasper Cornelia
Institute of Cell and Tissue Culture Technologies, Department of Biotechnology, University of Natural Resources and Life Sciences BOKU Vienna, 1190 Vienna, Austria.
Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
Bioengineering (Basel). 2022 Feb 6;9(2):66. doi: 10.3390/bioengineering9020066.
Mesenchymal stem cells (MSCs) are primary candidates in tissue engineering and stem cell therapies due to their intriguing regenerative and immunomodulatory potential. Their ability to self-assemble into three-dimensional (3D) aggregates further improves some of their therapeutic properties, e.g., differentiation potential, secretion of cytokines, and homing capacity after administration. However, high hydrodynamic shear forces and the resulting mechanical stresses within commercially available dynamic cultivation systems can decrease their regenerative properties. Cells embedded within a polymer matrix, however, lack cell-to-cell interactions found in their physiological environment. Here, we present a "semi scaffold-free" approach to protect the cells from high shear forces by a physical barrier, but still allow formation of a 3D structure with in vivo-like cell-to-cell contacts. We highlight a relatively simple method to create core-shell capsules by inverse gelation. The capsules consist of an outer barrier made from sodium alginate, which allows for nutrient and waste diffusion and an inner compartment for direct cell-cell interactions. Next to capsule characterization, a harvesting procedure was established and viability and proliferation of human adipose-derived MSCs were investigated. In the future, this encapsulation and cultivation technique might be used for MSC-expansion in scalable dynamic bioreactor systems, facilitating downstream procedures, such as cell harvest and differentiation into mature tissue grafts.
间充质干细胞（MSCs）因其具有引人关注的再生和免疫调节潜能，成为组织工程和干细胞治疗的主要候选细胞。它们自组装成三维（3D）聚集体的能力进一步改善了其某些治疗特性，例如分化潜能、细胞因子分泌以及给药后的归巢能力。然而，市售动态培养系统中的高流体动力剪切力以及由此产生的机械应力会降低它们的再生特性。然而，嵌入聚合物基质中的细胞缺乏在其生理环境中发现的细胞间相互作用。在此，我们提出一种“半无支架”方法，通过物理屏障保护细胞免受高剪切力影响，但仍允许形成具有体内样细胞间接触的3D结构。我们重点介绍了一种通过反向凝胶化创建核壳胶囊的相对简单方法。这些胶囊由海藻酸钠制成的外部屏障组成，该屏障允许营养物质和废物扩散，以及一个用于直接细胞间相互作用的内部隔室。除了对胶囊进行表征外，还建立了收获程序，并研究了人脂肪来源的间充质干细胞的活力和增殖情况。未来，这种封装和培养技术可能用于在可扩展的动态生物反应器系统中扩增间充质干细胞，促进下游程序，如细胞收获和分化为成熟组织移植物。
