Collagen microencapsulation of human mesenchymal stem cells – An in vitro model for autophagy modulation studies

Abstract

Mesenchymal stem cells (MSCs) are adult stem cells derived from clinically feasible sources such as bone marrow and adipose tissues. MSC-based therapeutic strategies have been developed attempting to treat degenerative diseases such as osteoarthritis. However, a critical problem to be tackled before clinical translation is the senescence problem of MSCs. Loss of autophagy is a hallmark of ageing. Deficient autophagy associates with reduced regenerative capacity in aged stem cells. We found that MSCs from aged patients showed poor proliferative potential and rapid ageing. We have previously developed a collagen microencapsulation technology, entrapping hMSCs in nanofibrous collagen meshwork. This leads to the formation of a physiologically relevant 3D microtissue model. Preliminary data showed that when MSCs are microencapsulated, major autophagy markers such as LC3 were significantly downregulated as compared with the 2D monolayer expanded cells. This suggests that the microencapsulation model is more physiologically relevant. More interestingly, when we allow the MSCs to transmigrate from the autophagy-inhibited collagen microspheres, upregulation of the major autophagy markers and increased metabolic rate were noted. These data prompt us to use the 3D microencapsulation model as an in vitro model to study autophagy modulation for aged MSCs. This project will impact future development of stem cell based therapy for tissue engineering and regenerative medicine.