Advancing Mesenchymal Stromal Cell-Dressing Therapy for Myocardial Repair: Application Expansion, Technical Innovation and Mechanistic Investigations (renewal)

We have developed a novel cell therapy technology, termed amniotic membrane-derived mesenchymal stromal cell (AMSC)-dressing therapy, through the current BHF Programme. This method of epicardial placement of instantly-produced, bi-layered, self-adhesive films containing AMSCs substantially augments the therapeutic efficacy of MSC-based therapy for ischaemic cardiomyopathy through improvement of both quantity and quality of donor cell engraftment. This advanced therapy is user-friendly and has a great potential to be a widely-adopted treatment for cardiac repair. Based on our solid preclinical evidence, a clinical trial of this therapy for ischaemic cardiomyopathy will initiate soon. This proposed Programme aims to further develop this research line through (1) expansion of the use of AMSC-dressing therapy to dilated cardiomyopathy; (2) development of hydrogel-aided intrapericardial AMSC injection as an advanced version of AMSC-dressing therapy, which will achieve an equivalent therapeutic efficacy with reduced invasiveness; (3) further mechanistic investigations with original ideas to elucidate the “secondary paracrine effect” (AMSC-exosomes augment reparative macrophages, which in turn release necessary exosomes to promote cardiac repair). This UK-based unique technology will contribute to advancing the clinical success of cell therapy for heart failure and also provide new biological information on MSCs, myocardial repair, macrophages and exosomes.