Tissue Beads: Tissue-Specific Extracellular Matrix Microbeads to Potentiate Reprogrammed Cell-Based Therapy

Microbeads have been utilized as efficient cell culture carriers and injectable scaffolds for cell transplantation. However, various polymers currently used to generate microbeads have limited applicability due to loss of biological functions and tissue-specific effects. Here, a tissue bead platform is reported that can provide a tissue-specific microenvironment to facilitate cell culture and potentiate cell therapy. Using a flow-focusing microfluidic device, uniform-sized tissue microbeads are fabricated with extracellular matrix (ECM) from various decellularized tissues. The tissue microbeads are tested for tissue-specific encapsulation of induced hepatic (iHep), induced cardiac (iCar), and induced myogenic (iMyo) cells, which are directly reprogrammed from mouse primary fibroblasts. Tissue-specific microbeads significantly enhanced the viability, lineage-specific maturation, and functionality of each type of reprogrammed cell, as compared to functionality when using conventional microbeads from a single ECM component (collagen). Finally, tissue microbeads are confirmed to mediate the successful in vivo engraftment of reprogrammed cells (iHep and iMyo) after transplantation, potentiating cell therapy and promoting functional tissue regeneration in tissue defective animal models. The study suggests that the use of a decellularized tissue matrix combined with a microfluidic technique can be employed to produce tissue-specific ECM microbeads with increased versatility and efficacy for reprogrammed cell-based therapy.