Fluorescent Conjugated Polymer Nanovector for In Vivo Tracking and Regulating the Fate of Stem Cells for Restoring Infarcted Myocardium.

Abstract Stem cell therapy holds great promise for cardiac regeneration. However, the lack of ability to control stem cell fate after in vivo transplantation greatly restricts its therapeutic outcomes. MicroRNA delivery has emerged as a powerful tool to control stem cell fate for enhanced cardiac regeneration. However, the clinical translation of therapy based on gene-transfected stem cells remains challenging, due to the unknown in vivo behaviors of stem cells. Here, we developed a nano-platform (i.e., PFBT@miR-1-Tat NPs) that can achieve triggered release of microRNA-1 to promote cardiac differentiation of mesenchymal stem cells (MSCs), and long-term tracking of transplanted MSCs through bright and ultra-stable fluorescence of conjugated polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT). We found that PFBT@miR-1-Tat NP-treated MSCs significantly restored the infarcted myocardium by promoting stem cell cardiac differentiation and integration with the in situ cardiac tissues. Meanwhile, MSCs without gene delivery improved the infarcted heart functions mainly through a paracrine effect and blood vessel formation. The developed conjugated polymer nanovector should be a powerful tool for manipulating as well as revealing the fate of therapeutic cells in vivo, which is critical for optimizing the therapeutic route of gene and cell combined therapy and therefore for accelerating clinical translation.