Microencapsulated macrophages releases conditioned medium able to prevent epithelial to mesenchymal transition

Abstract

Epithelial to mesenchymal transition (EMT) has emerged as a key process in the development of renal fibrosis. In fact, EMT-derived fibroblasts contribute to the progression of chronic renal disease. In addition, anti-inflammatory M2 macrophages have exhibited a great influence on renal fibrosis. However, because of the high impact that the inputs of different environmental cytokines have on their phenotype, macrophages can easily lose this property. We aim to known if microencapsulated macrophages on M2-inducing alginate matrices could preserve macrophage phenotype and thus release factors able to act on epithelial cells to prevent the epithelial differentiation towards mesenchymal cells. We reproduced an in vitro model of EMT by treating adipose-derived stem cells with all-trans retinoic acid (ATRA) and induced their transformation toward epithelia. Dedifferentiation of epithelial cells into a mesenchymal phenotype occurred when ATRA was retired, thus simulating EMT. Results indicate that induction of M2 phenotype by IL-10 addition in the alginate matrix produces anti-inflammatory cytokines and increases the metabolic activity and the viability of the encapsulated macrophages. The released conditioned medium modulates EMT and maintains healthy epithelial phenotype. This could be used for in vivo cell transplantation, or alternatively as an external releaser able to prevent epithelial to mesenchymal transformation for future anti-fibrotic therapies.

Advancing Cell-Instructive Biomaterials Through Increased Understanding of Cell Receptor Spacing and Material Surface Functionalization

“…This includes fibrosis [ 61 ] and cancer [ 62 ]. Fibrosis is a major hurdle in regenerative medicine, as introducing foreign materials into the body can induce fibrosis, negatively impacting the biochemical and mechanical properties of the regenerated tissue [ 63 , 64 ]. Recent studies using materials aimed at clustering cadherins are exploring their use in improved tissue implantation without inducing fibrosis.…”

3D Printed porous polyamide macrocapsule combined with alginate microcapsules for safer cell-based therapies

“…The molecular weight cut-off of this semi-permeable membrane lies in approximately 60–70 KDa, and, therefore, the entrance of IgG and IgM antibodies of the humoral immunity as well as the cells involved in the cellular immunity response are blocked. However, lower molecules necessary for cell survival such as glucose (180 Da) and carbon dioxide (44 Da) and secretary proteins from cells such as growth factors (6–50 KDa) can easily pass 27 , 28 . On the other hand, the external macro-device would maintain the total volume of the loaded microcapsules in the implantation site (Fig.…”