Stem Cell Therapy for Congenital Heart Defect Begins Pivotal Trial Phase

Key details

• New clinical phase: A stem cell therapy called laromestrocel has entered a pivotal Phase 2b clinical trial to treat hypoplastic left heart syndrome (HLHS), a congenital defect where the left heart is severely undeveloped.[1]
• Standard of care: Treatment for HLHS typically requires a three-stage surgical plan (Norwood, Glenn, and Fontan procedures) to bypass the left side of the heart, as the condition is fatal without intervention.
• Regenerative potential: The trial injects mesenchymal stem cells (MSCs) during the Glenn procedure to strengthen the heart, potentially delaying or eliminating the need for a heart transplant.
• Promising safety profile: Phase 1 trials showed 100% survival and transplant-free status five years post-treatment, exceeding historical averages for this condition.

What is hypoplastic left heart syndrome?

Hypoplastic left heart syndrome (HLHS) is a congenital heart defect in which the left side of the heart, which is responsible for pumping oxygenated blood through the body, does not develop properly in the womb. Because the left side is small and undeveloped, it cannot perform its function.

During pregnancy, the baby’s circulatory system relies on temporary connections to bypass the lungs:

• Foramen ovale: a hole between the two sides of the heart.
• Ductus arteriosus: a duct connecting the pulmonary (lung) artery to the body artery (aorta).

Normally, these connections close shortly after birth, as they are no longer needed after a baby is born and begins to breathe for themselves. In babies with HLHS, however, these connections are the only pathway for oxygenated blood to reach the body. Once they close, the right side of the heart cannot maintain circulation alone, leading to critical symptoms in the first hours or days after birth, including:

• Cyanosis: a bluish tint to the skin due to poor oxygen levels.
• Circulatory issues: cold hands and feet, lethargy and poor pulse.
• Respiratory distress: trouble breathing.

If left untreated, HLHS is fatal.[2][3][4][5]

How is HLHS treated?

Babies born with HLHS require a series of surgical procedures to bypass the left side of the heart and increase blood flow to the body. This is typically done in three stages:[5][6]

• The Norwood procedure (first two weeks of life) rebuilds the aorta and connects it to the heart’s lower right chamber (ventricle), then connects either the aorta or the right ventricle to the pulmonary artery. This enables the right side of the heart to pump blood to the whole body.[7]
• The bidirectional Glenn procedure (4-6 months of age) removes the connection between the pulmonary artery and the aorta, and connects instead the pulmonary artery and the large vein that drains blood from the head and the arms (superior vena cava). This procedure allows oxygen-poor blood returning from the upper body to flow directly to the lungs, lessening the strain on the heart and improving oxygenated blood flow.[8]
• The Fontan procedure (3-4 months of age) connects the vein that drains blood from the lower body and legs (inferior vena cava) to the pulmonary artery, further improving oxygenated blood flow.[9]

These surgeries allow many babies born with HLHS to survive into childhood and beyond.[4] However, the condition puts extra strain on the heart, eventually leading to heart failure and the need for a heart transplant.[1][10] As with all transplants, this is limited by the scarcity of available hearts, leading to lengthy waiting lists. In the specific case of HLHS, the issue is further complicated by common support treatments for heart failure being more technically challenging due to the heart only having one ventricle.[11]

How could stem cells therapy help HLHS patients?

The investigational therapy, laromestrocel, utilizes mesenchymal stem cells (MSCs) derived from the bone marrow of healthy donors to boost heart function. It is administered directly into the heart muscle during the Glenn procedure.[10]

This therapy is designed as an addition to surgery, not a replacement. The MSCs offer two primary benefits:

1. Regeneration: They may stimulate the growth of new blood vessels and activate the heart’s own regenerative capabilities.
2. Anti-inflammatory effects: Powerful anti-inflammatory properties help strengthen the heart muscle.

The goal is to improve the heart’s performance enough to delay heart failure, thereby delaying the need for a transplant and even, potentially, eliminating it altogether.[1]

What is the current status of the HLHS stem cell clinical trial?

The therapy has advanced to a pivotal phase 2b trial following promising results in an earlier phase 1 trial.

In the phase 1 trial, the treatment proved to be safe, with no major adverse cardiac events nor treatment-related infections occurring.[10][12] Notably, all patients remained alive and transplant-free five years after treatment, an outcome better than historical averages.[1][13]

The current phase 2b is a placebo-controlled, double-blinded study involving 40 babies with HLHS recruited across top paediatric heart centres in the United States:

• Treatment group: 20 babies will be randomly assigned to receiving the stem cell therapy together with the Glenn procedure.
• Control group: 20 babies will undergo the standard Glenn procedure only.
• Timeline: Initial results are expected within a year, with a longer-term follow-up of up to five years also planned.[1][14]

Why is stem cell banking important for future therapies?

The rapid advancement of regenerative medicine highlights the critical importance of preserving stem cells, such as those found in the umbilical cord, for potential future use. Indeed, stem cells from various sources, including not only bone marrow, but also the umbilical cord, are being trialled to help strengthen the heart of HLHS sufferers; the best point during the existing course of surgical treatment at which to administer the stem cells is also being investigated.[15]

Moreover, researchers are also trialling laromestrocel as a potential therapy for other conditions that could benefit from the anti-inflammatory and regenerative effects of MSCs, including Alzheimer’s and aging frailty.[12]

For children born today, access to these emerging therapies may depend on the availability of diverse stem cell sources. While bone marrow can be harvested later in life, other potent sources like the umbilical cord and placenta are only available for collection during the few minutes immediately following birth. To learn more about how you could preserve this precious resource for your child’s potential future use, fill in the form below to request our free guide.

References

[1] Cardiovascular Business. (2025). First study of its kind to focus on new therapy for hypoplastic left heart syndrome. https://cardiovascularbusiness.com/topics/clinical/cardiac-surgery/first-study-its-kind-focus-new-therapy-hypoplastic-left-heart-syndrome

[2] Little Hearts Matter. (2021). Hypoplastic Left Heart Syndrome. https://www.lhm.org.uk/hypoplastic-left-heart-syndrome/

[3] Mayo Clinic (2025). Hypoplastic left heart syndrome – symptoms and causes. https://www.mayoclinic.org/diseases-conditions/hypoplastic-left-heart-syndrome/symptoms-causes/syc-20350599

[4] Cleveland Clinic (2022). Hypoplastic Left Heart Syndrome (HLHS): Causes, Symptoms, Surgeries & More. https://my.clevelandclinic.org/health/diseases/12214-hypoplastic-left-heart-syndrome-hlhs

[5] CDC (2024). About Hypoplastic Left Heart Syndrome (HLHS). https://www.cdc.gov/heart-defects/about/hypoplastic-left-heart-syndrome.html

[6] Mayo Clinic (2018). Hypoplastic left heart syndrome – Diagnosis and treatment. https://www.mayoclinic.org/diseases-conditions/hypoplastic-left-heart-syndrome/diagnosis-treatment/drc-20350605

[7] KidsHealth (2018). Hypoplastic Left Heart Syndrome Surgery: The Norwood Procedure (for Parents). https://kidshealth.org/en/parents/norwood.html

[8] KidsHealth (2018). Hypoplastic Left Heart Syndrome Surgery: The Glenn Procedure (for Parents). https://kidshealth.org/en/parents/glenn.html

[9] KidsHealth (2018). Hypoplastic Left Heart Syndrome Surgery: The Fontan Procedure (for Parents). https://kidshealth.org/en/parents/fontan.html

[10] Kaushal, S., et al. (2023). Intramyocardial cell-based therapy with Lomecel-B during bidirectional cavopulmonary anastomosis for hypoplastic left heart syndrome: the ELPIS phase I trial. European Heart Journal Open, 3(2). doi:https://doi.org/10.1093/ehjopen/oead002

[11] Williams, K., Khan, A., Lee, Y.-S. and Hare, J.M. (2023). Cell-based therapy to boost right ventricular function and cardiovascular performance in hypoplastic left heart syndrome: Current approaches and future directions. Seminars in Perinatology, [online] 47(3), p.151725. doi:https://doi.org/10.1016/j.semperi.2023.151725

[12] Longeveron (2022). Clinical Trials. https://longeveron.com/clinical-trials/

[13] Kaushal, S., et al. (2023). Abstract 17067: Long-Term Transplant-Free Survival is Improved in Hypoplastic Left Heart Syndrome With Cell-Based Therapy. Circulation, 148(Suppl_1). doi:https://doi.org/10.1161/circ.148.suppl_1.17067

[14] UTHealth Houston (2023). ELPIS II Study. https://sph.uth.edu/research/centers/ccct/elpis/

[15] Xiao, R., Darr, H., Khan, Z. and Xiao, Q. (2025). Updated Applications of Stem Cells in Hypoplastic Left Heart Syndrome. Cells, 14(17), p.1396. doi:https://doi.org/10.3390/cells14171396