Intramyocardial injection of allogeneic human induced pluripotent stem cell-derived cardiomyocytes in advanced ischemic heart failure: an early-stage randomized trial

Efficacy of multi-layered human iPS cell-derived cardiovascular cell sheets in a pacing-induced canine dilated cardiomyopathy model

IHJ-301 significantly improved multiple parameters of cardiac function, providing preclinical evidence that IHJ-301 could offer a promising therapeutic option for DCM.

Human iPSC-cardiomyocyte-aggregate cell therapy in non-human primates and correlation of heart recovery with contractile and electrophysiological cardiomyocyte properties

This study demonstrates the successful production and injection of human induced pluripotent stem cell cardiomyocyte aggregates into infarcted cynomolgus monkey hearts, resulting in substantial, structured human grafts three months after cell transplantation, and uncoupling of cardiomyocyte production from transplantation is demonstrated.

Poor survival after myocardial infarction in immune deficient NXG B2m mice is alleviated by transplantation of induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) formulated as spheres, but not single cells

Induced Pluripotent Stem Cells and 3D Bioprinting Strategies for Cardiac Regeneration After Myocardial Infarction

Cardiovascular disease is the leading cause of death worldwide, often resulting in a myocardial infarction (MI), which can lead to irreversible cell death and heart failure (HF). While advances in bioengineering and regenerative medicine offer promising solutions for patients, traditional heart transplantations are limited due to a shortage of organ donors. To address this issue, differentiating induced pluripotent stem cells (iPSCs) into cardiomyocytes via signaling pathways can provide a patientspecific source of functional cardiomyocytes, and as a long-term goal it may be capable of replacing damaged myocardial tissue. This study evaluates the role of iPSCs and different biofabrication methods, such as bioprinting, used to create ventricular constructs and cardiac patches that support injured regions of the heart post-MI. However, for patients with HF, bioprinting a whole-heart construct is being explored as a future objective and is necessary to restore cardiac function when cardiac patches or ventricular constructs are not sufficient. Despite the progress made in the field, few studies have addressed the need to improve bioprinting vascular networks, adopt appropriate bioinks, and reduce costs for iPSC differentiation and bioprinting technologies. If successful, this work can eventually mitigate symptoms post-MI or contribute to addressing HF solutions, offering patients a new quality of life.

Clinical landscape of human pluripotent stem cell-derived cardiomyocyte therapy.

The pathophysiological rationale for cell-based therapy in heart failure with reduced ejection fraction is summarized, and the preclinical foundations of distinct hPSC-derived product formats are examined, including cell suspensions, epicardial sheets, engineered heart muscle, and cardiac spheroids, each with distinct tradeoffs and translational considerations.

Extracellular vesicle secretome from mesenchymal stromal cells prevents post-ischemic heart failure by targeting cardiac fibrosis.

Myocardial ischemia-reperfusion (MIR) injury drives adverse remodeling and heart failure after ST-elevation myocardial infarction (STEMI), yet no therapy directly targets the fibrotic response. Here, we developed a good manufacturing practice-compatible extracellular vesicle (EV)-enriched secretome from bone marrow mesenchymal stromal cells and identified a laminin-521-based production strategy suitable for clinical translation. The EV-enriched secretome exhibited in vitro immunomodulatory activity, and in murine MIR-injury models, treatment preserved left ventricular ejection fraction, reduced platelet-derived growth factor receptor beta (PDGFRβ)-associated myofibroblast activation quantified by positron emission tomography (PET) imaging, attenuated fibrosis, and promoted reparative macrophage polarization. In a clinically relevant porcine ischemia-reperfusion model, intracoronary administration was cardioprotective. We further developed a clinically approved PDGFRβ-targeted PET-imaging platform for longitudinal assessment of fibrotic activity in STEMI patients, where preliminary observations suggest that myofibroblast activation persists for up to 2 months after STEMI in selected patients. Together, these findings establish a translational therapeutic-diagnostic framework for individualized management of MIR injury.