Angiogenic and reparative potency of a human cardiac CD90- mesenchymal subpopulation in heart ischemic model.

BACKGROUND

Despite recent significant therapeutic progress, cardiovascular diseases (CVD) remain an unmet clinical, economic, and social burden worldwide. Cell-based therapies have been proposed as therapeutic strategies, however, the overall efficacy was modest.

OBJECTIVE

We aimed to fully characterize a novel subpopulation of CD90- mesenchymal cells derived from human heart tissue (hCmPC90-) and evaluate its ability to induce cardiac tissue repair and functional recovery.

METHODS

We performed a comprehensive phenotypic characterization of the hCmPC90- by flow cytometry and RNA sequencing. A direct comparison of hCmPC90- with previously clinically tested bone marrow- and cardiac-derived cell types, has been conducted both in vitro by means of various assays of angiogenic potency, and in vivo, by testing the ability to ameliorate left ventricular function in a mouse model of acute myocardial infarction (AMI).

RESULTS

hCmPC90- showed distinct surface markers and transcriptional phenotype compared with unselected mesenchymal heart cells (hCmPCs) and the positive CD90 counterpart (hCmPC90+). When human hCmPC90-, hCmPC90+, hCmPC, cardiosphere-derived cells (CDCs), and bone marrow-derived CD34+ cells were functionally tested in vitro, hCmPC90- revealed a superior endothelial differentiation ability, higher anti-inflammatory, cardio-protective capacity, and angiocrine activity. Moreover, hCmPC90- showed specific immune-privileged features. When intramyocardially delivered into infarcted mouse hearts, hCmPC90- outperformed three weeks after injection other clinical-grade cell types, as for left ventricular (LV) function and adverse LV remodeling recovery, infarct size reduction, and vascular density augmentation.

CONCLUSION

hCmPC90- shows a superior biological potency which deserves clinical exploitation as an advanced therapy medicinal product in the context of refractory ischemic heart disease.