ABSTRACT
BACKGROUND@#Mesenchymal stem cells (MSCs) are used for tissue regeneration due to their wide differentiation capacity and anti-inflammatory effects. Extracellular vesicles (EVs) derived from MSCs are also known for their regenerative effects as they contain nucleic acids, proteins, lipids, and cytokines similar to those of parental cells. There are several studies on the use of MSCs or EVs for tissue regeneration. However, the combinatorial effect of human MSCs (hMSCs) and EVs is not clear. In this study, we investigated the combinatorial effect of hMSCs and EVs on cartilage regeneration via co-encapsulation in a hyaluronic-acid (HA)-based hydrogel. @*METHODS@#A methacrylic-acid-based HA hydrogel was prepared to encapsulate hMSCs and EVs in hydrogels. Through in vitro and in vivo analyses, we investigated the chondrogenic potential of the HA hydrogel-encapsulated with hMSCs and EVs. @*RESULTS@#Co-encapsulation of hMSCs with EVs in the HA hydrogel increased the chondrogenic differentiation of hMSCs and regeneration of damaged cartilage tissue compared with that of the HA hydrogel loaded with hMSCs only. @*CONCLUSION@#Co-encapsulation of hMSCs and EVs in the HA hydrogel effectively enhances cartilage tissue regeneration due to the combinatorial therapeutic effect of hMSCs and EVs. Thus, in addition to cartilage tissue regeneration for the treatment of osteoarthritis, this approach would be a useful strategy to improve other types of tissue regeneration.
ABSTRACT
Alzheimer’s disease (AD) is the most common cause of neurodegeneration. It is characterized by deposits of amyloid beta (Aβ) plaques and impaired memory. Microglia are associated with AD. They are activated in the AD brain and AD models. However, the exact role of microglia has not been established. We thus investigated the role of microglia in AD models using a primary culture and an ex-vivo assay. We showed that oligomerized Aβ is toxic to neurons in the primary culture. In the ex-vivo assay, a microglial cell line removed amyloid plaques in the brain of 5XFAD (AD model) mice. To verify if microglia can be protective for the neuron, we co-cultured neurons with primary microglia and treated them with Aβ. The loss of neurons, induced by amyloid toxicity, was attenuated by co-cultured microglia. Taken together, our data suggest that microglia promote neuronal survival by phagocytic clearance of Aβ in AD models.