Magnetoresponsive stem cell spheroid-based cartilage recovery platform utilizing electromagnetic fields

Abstract

Mesenchymal stem cells (MSCs) provide a promising source for cartilage tissue regeneration strategies. The use of MSCs for such strategies, however, remains challenging due to the low targeting and low chondrogenic differentiation efficiency of these cells to the desired site. In an attempt to overcome such problems, we propose the use of a magnetoresponsive stem cell spheroid (MR-SCS)-based cartilage recovery platform that allows for precise targeting using an electromagnetic actuation (EMA) system to provide magnetic control and low-frequency electromagnetic field (LF-EMF) to allow for biophysical stimulation to promote chondrogenic differentiation. MR-SCSs were fabricated from mouse-derived MSCs that were labeled with magnetic nanoparticles (MNPs) using 3D culture methods, and these particles exhibited no cytotoxicity and did not affect chondrogenic differentiation. Locomotion of MR-SCS that was mediated by the EMA system was successfully demonstrated in 3D phantom and ex vivo models. Additionally, LF-EMF stimulation of MR-SCS resulted in increased expression levels of cartilage specific markers, collagen type II, SOX9, and Aggrecan. Finally, histological evaluation revealed an apparent improvement in the regeneration of cartilage tissue in an ex vivo model of the porcine femur in response to LF-EMF stimulation. These results suggest that our experimental platform consisting of MR-SCSs that are subjected to EMA and LF-EMF stimulation may provide a promising therapeutic system for cartilage tissue regeneration.