Magnetically controlled microgelbots with stem cells for the treatment of interstitial cystitis.

Abstract

Stem cell therapy has been widely investigated for the treatment of chronic bladder diseases such as interstitial cystitis/bladder pain syndrome (IC/BPS). However, the delivery of stem cells into the bladder wall is limited due to the mucus layer lining the bladder wall and the frequent urination, leading to the fast clearance of stem cells from the bladder. Here, we report a soft microgelbot (μgelbot) composed of a magnetic nanochain embedded microgel in a tunable size and shape for the enhanced delivery of mesenchymal stem cells (MSCs) into the bladder wall through the mucus layer. In vitro penetration tests to optimize the shape of μgelbots show that the quadrangle shaped μgelbots effectively apply a shear force to the surrounding shear-thinning mucus layer for the enhanced penetration under a rotating magnetic field. After loading MSCs onto the μgelbot, we confirm the enhanced penetration and retention in the reconstructed mucus layer. Finally, we successfully demonstrate the paracrine effects of MSCs loaded μgelbots on chronic IC murine models, inhibiting the mast cell infiltration, collagen deposition, and bladder cell apoptosis. Taken together, we could confirm the feasibility of magnetically controlled μgelbots as a promising platform for the stem cell therapy of IC/BPS.