Stem Cell Therapy for Heart Failure

(HECTOR Trial)

Overseen By Joseph C. Wu, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Joseph C. Wu

Must be taking: Beta-blockers, ACE inhibitors

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Renal failure, Aortic stenosis, Arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical study will utilize a new cell therapy approach (Human embryonic stem cells derived cardiomyocytes or hESC-CMs) to improve survival and cardiac function in patients with chronic left ventricular dysfunction secondary to MI (Myocardial Infarction).

Will I have to stop taking my current medications?

The trial requires that you have been on a stable dose of certain heart medications, like beta-blockers and ACE inhibitors, for a specific period before joining. If you are on Coumadin, you will need to stop it 5 days before the procedure. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the treatment Human Embryonic Stem Cell-Derived Cardiomyocytes for heart failure?

Research shows that human embryonic stem cell-derived cardiomyocytes can improve heart function by replacing damaged heart cells and supporting heart repair processes. Studies in animal models have demonstrated their potential to survive long-term and prevent heart failure progression, offering hope for their use in treating heart conditions. ^{1 2 3 4 5}

Is stem cell therapy for heart failure safe?

The safety of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) for heart failure is still being studied, with some research focusing on potential side effects like arrhythmias (irregular heartbeats). While early studies in animals show promise, more research is needed to confirm safety in humans. ^{1 6 7 8 9}

How is the treatment using human embryonic stem cell-derived cardiomyocytes (hESC-CMs) for heart failure different from other treatments?

This treatment is unique because it uses human embryonic stem cells to create new heart cells that can integrate with the patient's heart, potentially repairing damaged tissue, unlike traditional treatments that rely on medication or mechanical devices. ^{1 5 10 11 12}

Eligibility Criteria

Adults aged 21-79 with chronic heart failure due to a past heart attack, who can undergo cardiac catheterization and have been on stable heart medication. They must not have severe allergies, organ transplants, life-limiting non-cardiac conditions, significant kidney/liver/blood issues, or be pregnant. Those with recent serious arrhythmias or certain heart devices are excluded.

Inclusion Criteria

My heart's pumping ability is reduced.

I have been on stable heart failure medication for the required time.

I was hospitalized recently or have high NT pro-BNP levels.

Exclusion Criteria

I have a health condition that may limit my life to less than a year.

I have a serious heart rhythm problem without a pacemaker or defibrillator.

I have experienced rejection of a transplanted organ or cells.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive varying doses of hESC-CMs to assess safety and establish the maximum tolerated dose

6-8 weeks

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiac MRI assessments

3 years

Regular follow-up visits for cardiac MRI and safety assessments

Treatment Details

Interventions

• Human Embryonic Stem Cell-Derived Cardiomyocyte

Trial Overview The trial is testing three doses (50M, 150M, and 300M cells) of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) for improving survival and heart function in patients with chronic left ventricular dysfunction after a myocardial infarction.

Participant Groups

Group I: Cohort 2 Active Control 1 Intervention

Medium dose (150M cells)

Group II: Cohort 3 Active Control 1 Intervention

High dose (300M cells)

Group III: Cohort 1 Active Control 1 Intervention

Low dose (50M cells)

Who Is Running the Clinical Trial?

Joseph C. Wu

Lead Sponsor

Trials

3

Recruited

40+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Findings from Research

In a porcine model of heart failure, transplantation of human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) significantly improved heart function compared to human embryonic stem cell-derived cardiomyocytes (hESC-CMs), as indicated by higher left ventricular ejection fraction and other hemodynamic measures after 8 weeks.

hiPSC-MSCs demonstrated a better safety profile than hESC-CMs, with no increase in proarrhythmia or tumor formation, and they enhanced angiogenesis and immune response, contributing to their superior efficacy in improving cardiac function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent immunomodulation and angiogenic effects of mesenchymal stem cells versus cardiomyocytes derived from pluripotent stem cells for treatment of heart failure. Liao, S., Zhang, Y., Ting, S., et al.[2020]

Engineered heart muscle (EHM) derived from human embryonic stem cells showed high engraftment rates and long-term survival in a rat model of chronic myocardial infarction, indicating potential for functional benefits in heart repair.

Importantly, the study demonstrated safety, as no teratomas or tumors were observed in any of the animals monitored, suggesting that EHM transplantation does not pose significant risks of tumor formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model. Riegler, J., Tiburcy, M., Ebert, A., et al.[2022]

Human embryonic stem cells (hESC) can be differentiated into cardiomyocytes, offering a promising source for myocardial cell replacement strategies in heart failure treatment.

The review highlights the structural and functional properties of hESC-derived cardiomyocytes and discusses the challenges and necessary steps for translating this technology into clinical applications for cardiac therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human embryonic stem cells for cardiomyogenesis. Habib, M., Caspi, O., Gepstein, L.[2008]

Cellular transplantation has shown promise in preclinical models of heart failure (HF) by improving heart function and promoting repair processes, largely due to the paracrine effects of transplanted stem cells.

Early human studies have yielded modest and inconsistent results, highlighting the need for further research to address challenges and optimize the use of stem cell therapies in managing cardiomyopathy and HF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular Therapy for Heart Failure. Psaltis, PJ., Schwarz, N., Toledo-Flores, D., et al.[2019]

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can be used to generate cardiomyocytes, which are heart cells that can potentially be used for cardiac therapies and drug testing, showing robust growth both in lab settings and in living organisms.

Recent studies have shown promising results for using these stem cell-derived cardiomyocytes in repairing heart damage and creating biological pacemakers, but challenges such as ensuring high purity of cardiac cells and preventing immune rejection still need to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac applications for human pluripotent stem cells. Shiba, Y., Hauch, KD., Laflamme, MA.[2022]

Human embryonic stem cells (hESCs) can be differentiated into cardiomyocytes (hESC-CMs), which possess cardiac-type action potentials and contractile properties, making them valuable for drug discovery and regenerative medicine.

Using hESC-CMs in in vitro assays can improve the predictive value of cardiac safety pharmacology tests, particularly in assessing the risk of proarrhythmic side effects, such as QT prolongation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human embryonic stem cell-derived cardiomyocytes: drug discovery and safety pharmacology. He, JQ., January, CT., Thomson, JA., et al.[2022]

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are emerging as a valuable tool for assessing cardiovascular safety in drug development, allowing for better hazard identification and risk assessment.

A recent User Meeting organized by Pluriomics highlighted the application of Pluricyte® Cardiomyocytes in cardiac safety assessments, emphasizing their role in supporting early decision-making in safety pharmacology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting cardiac safety using human induced pluripotent stem cell-derived cardiomyocytes combined with multi-electrode array (MEA) technology: A conference report. Mulder, P., de Korte, T., Dragicevic, E., et al.[2018]

Induced pluripotent stem cell (iPSC) technology allows for the unlimited production of functional human cardiomyocytes, which could potentially treat advanced cardiac failure by supplementing the heart with new cells.

Transplantation of iPSC-derived cardiomyocytes has shown promise in basic studies for improving cardiac function, but further pre-clinical research is needed to assess the safety and efficacy of this therapy before it can be applied in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building A New Treatment For Heart Failure-Transplantation of Induced Pluripotent Stem Cell-derived Cells into the Heart. Miyagawa, S., Fukushima, S., Imanishi, Y., et al.[2019]

Cardiac stem cell therapy using bone-marrow-derived stem cells shows promise for heart regeneration after heart attacks or in heart failure, and initial clinical data suggest it is safe with no increase in adverse events.

However, the confidence in safety is limited due to the small number of patients treated and lack of long-term follow-up, highlighting the need for more extensive data from ongoing and future trials to address potential safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone-marrow-derived cells for cardiac stem cell therapy: safe or still under scrutiny? Bartunek, J., Vanderheyden, M., Wijns, W., et al.[2007]

Transplanting human embryonic stem cell-derived cardiomyocytes (hESC-CMs) into rat hearts after a heart attack significantly improved heart function and reduced heart remodeling, demonstrating their potential for cardiac repair.

In contrast, injecting undifferentiated hESCs led to teratoma formation, while saline and non-cardiomyocyte derivatives resulted in further heart deterioration, highlighting the importance of using pre-differentiated cells for effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. Caspi, O., Huber, I., Kehat, I., et al.[2022]

The loss of functional heart cells (cardiomyocytes) leads to heart failure, and current treatments are limited since adult hearts cannot regenerate these cells.

This review explores the potential of using human embryonic stem cell-derived cardiomyocytes and vascular cells as a promising therapy for repairing heart tissue damaged by myocardial infarction and treating end-stage heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human embryonic stem cells for cardiovascular repair. Nir, SG., David, R., Zaruba, M., et al.[2019]

Human embryonic stem cells (hESCs) have the potential to differentiate into functional cardiomyocytes (hESC-CMs), which can integrate into the heart after transplantation, offering a promising alternative to traditional heart failure treatments.

Current cell-based therapies using adult bone marrow mesenchymal stem cells show favorable outcomes but are limited in their ability to regenerate heart tissue, highlighting the unique advantages of hESC-CMs in addressing heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human embryonic stem cell-derived cardiomyocytes for heart therapies. Siu, CW., Moore, JC., Li, RA.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Potent immunomodulation and angiogenic effects of mesenchymal stem cells versus cardiomyocytes derived from pluripotent stem cells for treatment of heart failure. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Human embryonic stem cells for cardiomyogenesis. [2008]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Cellular Therapy for Heart Failure. [2019]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Cardiac applications for human pluripotent stem cells. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Human embryonic stem cell-derived cardiomyocytes: drug discovery and safety pharmacology. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Predicting cardiac safety using human induced pluripotent stem cell-derived cardiomyocytes combined with multi-electrode array (MEA) technology: A conference report. [2018]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Building A New Treatment For Heart Failure-Transplantation of Induced Pluripotent Stem Cell-derived Cells into the Heart. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Bone-marrow-derived cells for cardiac stem cell therapy: safe or still under scrutiny? [2007]

10. United States pubmed.ncbi.nlm.nih.gov

Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Human embryonic stem cells for cardiovascular repair. [2019]

12. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Human embryonic stem cell-derived cardiomyocytes for heart therapies. [2019]