Aug 2026· Stem cell research & therapeutics· Vol 17· 0 citations· 42 references
Medicine
TL;DR
IHJ-301 significantly improved multiple parameters of cardiac function, providing preclinical evidence that IHJ-301 could offer a promising therapeutic option for DCM.
Abstract
Dilated cardiomyopathy (DCM) is a progressive, intractable disease that leads to heart failure. Heart transplantation is the only curative treatment; however, access is limited by donor scarcity. Induced pluripotent stem cell (iPSC)-based therapies are attracting attention for DCM, but suitable large-animal models and robust preclinical data have been limited. We generated multi-layered cardiovascular cell sheets from human iPSCs by combining cardiomyocytes with endothelial and stromal cells and overcoming stacking limits using interleaved gelatin hydrogel microspheres, yielding a thicker cardiac tissue-like construct (product code: IHJ-301). To enable rigorous testing in non-ischemic heart failure, we established a modified canine rapid-pacing heart failure model that maintains depressed function without mortality by continuing pacing at a slightly reduced rate after induction (Step-Down Pacing Heart Failure model). IHJ-301 was implanted epicardially onto the left ventricular surface via thoracotomy, and cardiac function was assessed by echocardiography and right-heart catheterization. After 4 weeks of rapid pacing (230 ± 10 bpm), left ventricular ejection fraction (LVEF) was reduced from 77.8 ± 1.1% (pre-pacing) to 44.9 ± 1.9% (n = 11) (0 W). Continued pacing at 210 ± 10 bpm for additional 4 weeks resulted in no mortality and maintained depressed function (4 W LVEF 47.3 ± 2.6%). IHJ-301 was implanted at 0 W. At 4 weeks post-implantation (4 W), all animals in the IHJ-301 group (n = 5) showed greater functional improvement than sham (n = 6). Absolute changes from 0 W to 4 W were: ΔLVEF (%) 9.38 ± 1.47 vs. 1.90 ± 0.34; Δfractional shortening (%) 4.84 ± 0.75 vs. 0.97 ± 0.18; stroke volume (mL/beat) 1.21 ± 1.26 vs. −2.99 ± 0.60; cardiac output (L/min) 0.19 ± 0.19 vs. −0.58 ± 0.12 (all p < 0.05). We established a non-ischemic large-animal heart failure model that sustains depressed function for one month, enabling clear therapeutic readouts. IHJ-301 significantly improved multiple parameters of cardiac function, providing preclinical evidence that IHJ-301 could offer a promising therapeutic option for DCM.
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.
Byron W H Mui, E. Neofytou, Joseph C. Wu· Cell Reports Medicine· 0 citations
Primary efficacy analyses indicated that cell transplantation provided significantly greater improvements in 6-min walk distance, global myocardial perfusion and relative wall thickening and relative wall thickening compared with coronary artery bypass grafting alone.
He Zhang, P. Menasché, Jia-Hao Fan et al.· Nature Medicine· 0 citations
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.
N. Shenoy· American Journal of Student...· 0 citations
Cardiovascular disease remains the leading cause of global mortality, in part because the heart has limited regenerative capacity. Human-induced pluripotent stem cells (hiPSCs) offer a scalable, patient-specific platform for modeling heart disease, advancing drug discovery, and developing regenerative therapies. This review evaluates recent developments in hiPSC technology, beginning with the generation of patient-specific models of inherited arrhythmias and cardiomyopathies. We examine progress in directing hiPSCs into specialized lineages, including cardiomyocytes, pacemaker cells, and Purkinje fibers, by highlighting key developmental signaling pathways and transcriptional regulators. Furthermore, we discuss emerging strategies for cell and therapeutic delivery, such as bioengineered patches and hydrogels, and address key challenges in cell maturation and functional integration. Finally, we review current clinical trials assessing the safety of hiPSC-based treatments for heart failure and conduction disorders. These advancements underscore the dual potential of hiPSCs as essential research tools and as aspirational therapeutic resources.
Berra Koskulu, Tabish Ali, Ilkin Tetik-Altintop et al.· Journal of the American Hear...· 0 citations
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.
I. Gruh, Andreas Martens, S. Cebotari et al.· Nature Communications· 0 citations
Dilated cardiomyopathy (DCM) is the leading cause of heart transplantation, with a 50% risk of progression to heart failure within 5 years. Conventional disease modeling approaches fail to recapitulate the sophisticated function of the human heart. Alternatively, heart-on-a-chip (HOC) platforms enable real-time monitoring of disease progression and drug responses using miniaturized engineered heart tissues. Here, we developed a functional HOC model using patient-specific human induced pluripotent stem cells (hiPSCs), reprogrammed from the patients' blood samples. The chip contains two cell-seeding chambers with flexible silicone pillars to support tissue formation. Healthy and DCM hiPSCs were differentiated into cardiomyocytes, combined with an optimized ratio of human cardiac fibroblasts, encapsulated in a fibrin/Geltrex hydrogel (containing fluorescent beads), and seeded in the device chambers. The tissue gradually compacted and started beating spontaneously. Immunofluorescence assay revealed structural abnormalities in DCM tissues, including reduced cell alignment and elongation. The tissue functional responses (e.g., calcium transients and beating) were investigated after 2 weeks of culture, revealing arrhythmia-like behavior in DCM tissue and highlighting functional hallmarks of the disease. Finally, the platform was validated using norepinephrine to assess the functional responsiveness of the tissues. These results demonstrate the potential of this system for disease modeling and future patient-specific investigations.
Ali Mousavi, Ludovic Mouttet, Shihao Cui et al.· Advanced Healthcare Material...· 0 citations
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