Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy.

Despite major therapeutic advances, heart failure, as a non-communicable disease, remains a life-threatening disorder, with 26 million patients worldwide, causing more deaths than cancer. Therefore, novel strategies for the treatment of heart failure continue to be an important clinical need. Based on preclinical studies, allogenic human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches have been proposed as a potential therapeutic candidate for heart failure.

Engineered three-dimensional cardiac tissues maturing in a rotating wall vessel bioreactor remodel diseased hearts in rats with myocardial infarction.

A rotating wall vessel (RWV) bioreactor was constructed for growing massive functional cardiac constructs to recover the function of a distressed rat heart. Three-dimensional cardiac tissues were engineered by seeding human-induced pluripotent stem cell-derived cardiomyocytes on poly(lactic-co-glycolic acid) fiber sheets (3D-hiPSC-CTs) and cultured in the RWV bioreactor (RWV group) or under static conditions (control group). The tissues were transplanted into a myocardial infarction nude rat model, and cardiac performance was evaluated.

Clinical Outcomes of Autologous Stem Cell-Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy.

Background Clinical effectiveness of autologous skeletal cell-patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This clinical study aimed to determine the feasibility, safety, therapeutic efficacy, and the predictor of responders of this treatment in patients with nonischemic dilated cardiomyopathy. Methods and Results Twenty-four nonischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% on optimal medical therapy were enrolled.

Rapid and sensitive mycoplasma detection system using image-based deep learning.

A major concern in the clinical application of cell therapy is the manufacturing cost of cell products, which mainly depends on quality control. The mycoplasma test, an important biological test in cell therapy, takes several weeks to detect a microorganism and is extremely expensive. Furthermore, the manual detection of mycoplasma from images requires high-level expertise.

Cardiac fibrosis models using human induced pluripotent stem cell-derived cardiac tissues allow anti-fibrotic drug screening in vitro.

Drug efficacy assessment without using animals is important for development of cardiac fibrosis treatment. In this study, potential anti-fibrotic drugs were screened in a model of diseased myocardium using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and non-CM in in vitro and in vivo heart failure models. Cardiomyogenic differentiation was induced in hiPSC to generate cardiac tissue, including both iPSC-CM and non-CM expressing fibroblast markers.

Long-term outcomes of autologous skeletal myoblast cell-sheet transplantation for end-stage ischemic cardiomyopathy.

We evaluated the cardiac function recovery following skeletal myoblast cell-sheet transplantation and the long-term outcomes after applying this treatment in 23 patients with ischemic cardiomyopathy. We defined patients as "responders" when their left ventricular ejection fraction remained unchanged or improved at 6 months after treatment. At 6 months, 16 (69.

Role and therapeutic effects of skeletal muscle-derived non-myogenic cells in a rat myocardial infarction model.

Background: Transplantation of skeletal myoblast sheets is a promising strategy for the treatment of heart failure, and its therapeutic effects have already been proven in both animal disease models and clinical trials. Myoblast sheets reportedly demonstrate their therapeutic effects by producing many paracrine factors. Although the quality of processed cells for transplantation can be evaluated by the positive ratio of CD56, a myoblast marker, it is unclear which cell populations from isolated cells produce paracrine factors that have an impact on therapeutic effects, and whether these therapeutic effects are closely correlated with CD56-positive cells isolated from the skeletal muscle is also unclear.

Prostacyclin Analogue-Loaded Nanoparticles Attenuate Myocardial Ischemia/Reperfusion Injury in Rats.

Intravenously injected ONO-1301-containing nanoparticles (ONO-1301NPs), unlike an ONO-1301 solution, selectively accumulated in the ischemia/reperfusion (I/R)-injured myocardium of rats and contributed to the prolonged retention of ONO-1301 in the targeted myocardial tissue. In the ischemic area, proangiogenic cytokines were up-regulated and inflammatory cytokines were down-regulated upon ONO-1301NP administration. Consequently, ONO-1301NP-injected rats exhibited a smaller infarct size, better-preserved capillary networks, and a better-preserved myocardial blood flow at 24 h after I/R injury, compared with those in vehicle-injected or ONO-1301 solution-injected rats.

Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application.

Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay for the detection of these cells in hiPSC-CMs. The soft agar colony formation assay and cell growth analysis were unable to detect malignantly transformed cells in hiPSC-CMs.

Development of In Vitro Drug-Induced Cardiotoxicity Assay by Using Three-Dimensional Cardiac Tissues Derived from Human Induced Pluripotent Stem Cells.

An in vitro drug-induced cardiotoxicity assay is a critical step in drug discovery for clinical use. The use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is promising for this purpose. However, single hiPSC-CMs are limited in their ability to mimic native cardiac tissue structurally and functionally, and the generation of artificial cardiac tissue using hiPSC-CMs is an ongoing challenging.

Pivotal Role of Non-cardiomyocytes in Electromechanical and Therapeutic Potential of Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissue.

Although engineered cardiac tissues (ECTs) derived from induced pluripotent stem cells (iPSCs) are promising for myocardial regenerative therapy, the appropriate ratio of cardiomyocytes to non-cardiomyocytes is not fully understood. Here, we determined whether ECT-cell content is a key determinant of its structure/function, thereby affecting ECT therapeutic potential for advanced heart failure. Scaffold-free ECTs containing different ratios (25%, 50%, 70%, or 90%) of iPSC-derived cardiomyocytes were generated by magnetic-activated cell sorting by using cardiac-specific markers.

Development of vascularized iPSC derived 3D-cardiomyocyte tissues by filtration Layer-by-Layer technique and their application for pharmaceutical assays.

Unlabelled: In vitro development of three-dimensional (3D) human cardiomyocyte (CM) tissues derived from human induced pluripotent stem cells (iPSCs) has long been desired in tissue regeneration and pharmaceutical assays. In particular, in vitro construction of 3D-iPSC-CM tissues with blood capillary networks have attracted much attention because blood capillaries are crucial for nutrient and oxygen supplies for CMs. Blood capillaries in 3D-iPSC-CM tissues will also be important for in vitro toxicity assay of prodrugs because of the signaling interaction between cardiomyocytes and endothelial cells.

Cell-sheet therapy with omentopexy promotes arteriogenesis and improves coronary circulation physiology in failing heart.

Cell-sheet transplantation induces angiogenesis for chronic myocardial infarction (MI), though insufficient capillary maturation and paucity of arteriogenesis may limit its therapeutic effects. Omentum has been used clinically to promote revascularization and healing of ischemic tissues. We hypothesized that cell-sheet transplantation covered with an omentum-flap would effectively establish mature blood vessels and improve coronary microcirculation physiology, enhancing the therapeutic effects of cell-sheet therapy.

Myoblast sheet can prevent the impairment of cardiac diastolic function and late remodeling after left ventricular restoration in ischemic cardiomyopathy.

Background: Impairment of diastolic function and late remodeling are concerns after left ventricular restoration (LVR) for ischemic cardiomyopathy. This study aims to evaluate the effects of combined surgery of myoblast sheets (MS) implantation and LVR.

Methods: Rat myocardial infarction model was established 2 weeks after left anterior descending artery ligation.

The carboxyl terminal sequence of rat transporter associated with antigen processing (TAP)-like (ABCB9) is heterogeneous due to splicing of its mRNA.

Transporter associated with antigen processing (TAP)-like (TAPL) is a half-type ATP-binding cassette (ABC) transporter with sequence similarity to TAP1 and TAP2 and is highly conserved in mammals. Tissue distribution of the TAP family (TAP1, TAP2, TAPL) in rat was investigated using the semi quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). In young male rat, greater amounts of TAPL mRNA were detected in the brain and testis than in the thymus and intestine.