Tissue engineered constructs based on human adipose tissue derived stem cells and starch-based scaffolds for allogeneic approaches in tissue engineering and regenerative medicine

Abstract

The combination of natural-origin materials with mesenchymal stem cells (MSCs) from different sources have been suggested as suitable constructs for Tissue Engineering and Regenerative Medicine (TERM). Considering the importance of the host immune response to implanted tissue engineered constructs (TECs) and the immunomodulatory role assigned to MSCs and to adipose derived stem cells (ASCs) in particular, this work aimed at understanding the impact of SPCL-hASCs based TECs in the host inflammatory/immune system cells. The in vitro profile of inflammatory and anti-inflammatory cytokines expressed by macrophages (MØ) and dendritic cells (DCs), in contact with the scaffolds and the SPCL-hASCs based TECs, was evaluated by quantitative polymerase chain reaction (qRT-PCR). After 12h and 24h of direct contact, it was found that the level of expression of IL-10, IL-4, IL-6 and TNF both in MØ and DCs was bellow the detection limit. Additionally, the scaffolds and the SPCL-hASCs based TECs were intraperitoneally implanted in Balb/c mice in order to assess the expression of specific biomarkers of relevant immune cells through qRT-PCR, namely MØ, polymorphonuclear neutrophils (PMNS), B and T lymphocytes and DCs. Over the time course of the experiment comprising 7 days it was possible to verify that the SPCL scaffold seemed to trigger a less aggressive inflammatory response seen by a diminished expression of the evaluated immune cell markers when compared to the negative control. When comparing the TECs to the controls and the scaffold, TECs seemed to have the most promising results, that is, a diminished response throughout all the studied inflammatory/immune cell types was verified.<br>These findings suggest that the combination of SPCL scaffolds with hASCs offer a promise strategy for allogeneic approaches in the TERM field, also corroborating the reduced immunogenic properties of hASCs.