Treating Heart Failure With hPSC-CMs

Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes to Treat Severe Chronic Heart Failure

Heart failure has a high morbidity and mortality because the heart is one of the least regenerative organs in the human body. Drug treatments for heart failure manage symptoms but do not restore lost myocytes. Cellular replacement therapy is a potential approach to repair damaged myocardial tissue, restore cardiac function, which has become a new strategy for the treatment of heart failure. The purpose of this study is to assess the safety, feasibility and efficacy of intramyocardial delivery of cardiomyocytes at the time of coronary artery bypass grafting in patients with chronic heart failure.

Patients with heart failure will be treated with allogenic human pluripotent stem cell-derived cardiomyocytes ( hPSC-CM ) from healthy donors. The cells will be injected directly into the myocardium at time of coronary artery bypass grafting. Patients will be assessed at 1, 6 and 12 months after cell transplantation for safety, feasibility and efficacy.

Inclusion criteria

1. Aged 35-75 (including 35 and 75).
2. Have signed the Informed Consent Form (ICF).
3. Patients have chronic left ventricular dysfunction.
4. Patients have NYHA Class III-IV cardiac function even after improved medication for the treatment of advanced chronic heart failure.
5. Patients have indications for Coronary Artery Bypass Grafting.
6. 20% ≤ LVEF ≤ 45% as determined by echocardiogram (data collected up to 6 months prior to inclusion evaluation are valid; data collected within 1 month since a myocardial infarction are invalid).
7. Weakening or absence of segmental regional wall motion as determined by standard imaging.

Exclusion criteria

1. PRA ≥ 20% or DSA-positive.
2. Patient received ICD transplantation, CRT or similar treatment.
3. Patients with valvular heart disease or received heart valvular disease
4. Patients received treatment of percutaneous transluminal coronary intervention (PCI)
5. Patients with atrial fibrillation
6. Patients previously suffered sustained ventricular tachycardia or sudden cardiac death.
7. Baseline glomerular filtration rate <30ml/min/1.73m2.
8. Liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN.
9. Hematological abnormality: A hematocrit <25% as determined by HCT, white blood cell<2500/ul or platelet values <100000/ul without another explanation.
10. Known, serious radiographic contrast allergy, penicillin allergy, streptomycin allergy.
11. Coagulopathy (INR>1.3) not due to a reversible cause.
12. Contra-indication to performance of a MRI scan.
13. Recipients of organ transplant.
14. Clinical history of malignancy within 5 years (patients with prior malignancy must be disease free for 5 years).
15. Non-cardiac condition that limits lifespan <1 year.
16. On chronic therapy with immunosuppressant medication, such as glucocorticoid and TNFα antagonist.
17. Patients allergy to or cannot use immunosuppressant.
18. Serum positive for HIV, HBV, HCV, TP.
19. Currently enrolled other investigational therapeutic or device study.
20. Patients who are pregnant or breast feeding.
21. Other conditions that researchers consider not suitable to participate in this study.