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 lake of controllability in stem cell fate after in vivo transplantation greatly restricts the therapeutic outcomes of stem cell therapy. MicroRNA transfection 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 novel nano-platform (i.e., PFBT@miR-1-Tat NPs) that can achieve triggered release of microRNA-1 for promoting cardiac differentiation of mesenchymal stem cells (MSCs), and long-term tracking of transplanted MSCs through the bright and ultra-stable fluorescence of conjugated polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT). We found that PFBT@miR-1-Tat NP-transfected MSC treatment significantly restore infarcted myocardium through promoting stem cell cardiac differentiation and integration with the in-situ cardiac tissues. While, MSCs without gene transfection improve the infarcted heart functions mainly through paracrine effect and blood vessel formation. The developed conjugated polymer nanovector would be a powerful tool in 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.