Human tendon-derived cell sheets created by magnetic force-based tissue engineering hold tenogenic and immunomodulatory potential

Abstract

Cell sheet technology and magnetic based tissue engineering hold the potential to become instrumen- tal in developing magnetically responsive living tissues analogues that can be potentially used both for modeling and therapeutical purposes. Cell sheet constructions more closely recreate physiological niches, through the preservation of contiguous cells and cell-ECM interactions, which assist the cellular guidance in regenerative processes. We herein propose to use magnetically assisted cell sheets (magCSs) constructed with human tendon- derived cells (hTDCs) and magnetic nanoparticles to study inflammation activity upon magCSs exposure to IL-1 β, anticipating its added value for tendon disease modeling. Our results show that IL-1 βinduces an inflammatory profile in magCSs, supporting its in vitro use to en- lighten inflammation mediated events in tendon cells. Moreover, the response of magCSs to IL-1 βis mod- ulated by pulsed electromagnetic field (PEMF) stimulation, favoring the expression of anti-inflammatory genes, which seems to be associated to MAPK(ERK1/2) pathway. The anti-inflammatory response to PEMF together with the immunomodulatory potential of magCSs opens new perspectives for their applicability on tendon regeneration that goes beyond advanced cell based modeling.