Studies on alginate microcapsules embedding mesenchymal stem cell spheroids

Abstract

Stem cell transplantation has been recognized as a promising strategy for the treatment of various injuries or diseases. Stem cells, especially mesenchymal stem cells (MSCs), can release a variety of bioactive molecules which can, in turn, promote wound healing. However, the delivery of such stem cells into the body often causes several obstacles. First, the transplanted stem cells differently behave compared to those in vitro environments (e.g., two-dimensional monolayer culture). Conventionally cultured stem cells in the form of mono-layer lack cell-cell interactions, accompanied by limited cell-cell junction formation. In addition, stem cells are exposed to harsh environments during and after transplantation to target sites, such as the shear stress, attack by the immune system, and the oxidative stress. In this study, the simultaneous formation of stem cells microencapsulation and spheroid formation were revised to address the abovementioned problems. Dispersed MSCs were encapsulated in hyaluronic acid (HA)/alginate (Alg) core/shell microcapsules to protect cells from external stresses and to enhance their therapeutic activities. After 3 days of MSC encapsulation in HA@Alg microgels, MSCs in the HA core form spheroids, which were expected to exhibit enhanced survival and secretion of secretomes. The formation of cell-cell junctions of the MSC spheroids in the microcapsules was demonstrated. In conclusion, MSC spheroids in the HA@Alg microcapsules showed resistance against oxidative and shear stresses. The in situ production of MSC spheroids in hydrogel microcapsules will be beneficial to deliver or transplant MSCs for the regeneration of various tissues.