Membrane-Binding Adhesive Particulates Enhance the Viability and Paracrine Function of Mesenchymal Cells for Cell-Based Therapy.

ABSTRACT

Understanding the fundamental cell-material interactions is essential to designing functional materials for biomedical applications. Although mesenchymal stromal cells (MSCs) are known to secrete cytokines and exosomes that are effective to treat degenerative diseases, the inherent property of biomaterials to modulate the therapeutic function of MSCs remains to be investigated. Here, a multivalent cell-membrane adhesive conjugate was generated through polyamindoamine (PAMAM) and an oligopeptide, IKVAV, and the conjugate was further complexed with hyaluronic acid (HA). The adhesive particulates were used to coat the surface of adipose-derived mesenchymal stromal cells (Ad-MSCs) and studied in the MSC spheroid culture. The analysis showed that the adhesive complexes formed via PAMAM conjugates and HA significantly promoted the proliferation and the gene expression of pro-angiogenesis cytokines in MSCs; the production of anti-inflammatory miRNAs in exosomes could also be elevated. The transplantation of the Ad-MSCs primed with PAMAM-IKVAV/HA composite particulates in a rat myocardial infarction model further demonstrated the beneficial effects of membrane-binding materials on improving the cell retention and tissue angiogenesis. The new function of membrane-binding adhesive materials potentially provides useful ways to improve cell-based therapy.