These preliminary data suggest the feasibility and safety of autologous skeletal myoblast transplantation in severe ischemic cardiomyopathy, with the caveat of an arrhythmogenic potential. New-onset contraction of akinetic and nonviable segments suggests a functional efficacy that requires confirmation by randomized studies.

Cell therapy holds promise for tissue regeneration, including in individuals with advanced heart failure. However, treatment of heart disease with bone marrow cells and skeletal muscle progenitors has had only marginal positive benefits in clinical trials, perhaps because adult stem cells have limited plasticity. The identification, among human pluripotent stem cells, of early cardiovascular cell progenitors required for the development of the first cardiac lineage would shed light on human cardiogenesis and might pave the way for cell therapy for cardiac degenerative diseases. Here, we report the isolation of an early population of cardiovascular progenitors, characterized by expression of OCT4, stage-specific embryonic antigen 1 (SSEA-1), and mesoderm posterior 1 (MESP1), derived from human pluripotent stem cells treated with the cardiogenic morphogen BMP2. This progenitor population was multipotential and able to generate cardiomyocytes as well as smooth muscle and endothelial cells. When transplanted into the infarcted myocardium of immunosuppressed nonhuman primates, an SSEA-1 + progenitor population derived from Rhesus embryonic stem cells differentiated into ventricular myocytes and reconstituted 20% of the scar tissue. Notably, primates transplanted with an unpurified population of cardiac-committed cells, which included SSEA-1 -cells, developed teratomas in the scar tissue, whereas those transplanted with purified SSEA-1 + cells did not. We therefore believe that the SSEA-1 + progenitors that we have described here have the potential to be used in cardiac regenerative medicine.

This observation demonstrates the feasibility of generating a clinical-grade population of human ESC-derived cardiac progenitors and combining it within a tissue-engineered construct. While any conclusion pertaining to efficacy would be meaningless, the patient's functional outcome yet provides an encouraging hint. Beyond this case, the platform that has been set could be useful for generating different ESC-derived lineage-specific progenies.

This trial demonstrates the technical feasibility of producing clinical-grade hESC-derived cardiovascular progenitors and supports their short- and medium-term safety, thereby setting the grounds for adequately powered efficacy studies. (Transplantation of Human Embryonic Stem Cell-derived Progenitors in Severe Heart Failure [ESCORT]; NCT02057900).

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Shear wave imaging was evaluated for the in vivo assessment of myocardial biomechanical properties on ten open chest sheep. The use of dedicated ultrasonic sequences implemented on a very high frame rate ultrasonic scanner ( > 5000 frames per second) enables the estimation of the quantitative shear modulus of myocardium several times during one cardiac cycle. A 128 element probe remotely generates a shear wave thanks to the radiation force induced by a focused ultrasonic burst. The resulting shear wave propagation is tracked using the same probe by cross-correlating successive ultrasonic images acquired at a very high frame rate. The shear wave speed estimated at each location in the ultrasonic image gives access to the local myocardial stiffness (shear modulus μ). The technique was found to be reproducible (standard deviation ) and able to estimate both systolic and diastolic stiffness on each sheep (respectively μ(dias) ≈ 2 kPa and μ(syst) ≈ 30 kPa). Moreover, the ability of the proposed method to polarize the shear wave generation and propagation along a chosen axis permits the study the local elastic anisotropy of myocardial muscle. As expected, myocardial elastic anisotropy is found to vary with muscle depth. The real time capabilities and potential of Shear Wave Imaging using ultrafast scanners for cardiac applications is finally illustrated by studying the dynamics of this fractional anisotropy during the cardiac cycle.

The better preservation of LV geometry afforded by ADSC sheets is associated with increased survival and engraftment, which supports the concept of an epicardial delivery of cell-seeded biomaterials.

Although several facets of this manufacturing process still need to be improved, these data may yet provide a useful platform for the production of hESC-derived cardiac progenitor cells under safe and cost-effective GMP conditions.