Phase I Stem Cell Trial Results


Stem cells were first discovered by Russian-American scientist Alexander Maksimov in 1908. Sixty years later, the University of Minnesota performed the world’s first successful bone marrow transplant, which is now the standard treatment for blood cancers like leukemia.  In 1978, stem cells were discovered in umbilical cord blood (UCB), and in 2006, scientists created induced pluripotent stem cells which are cells that have been “reprogrammed” from one part of the body into a stem cell-like state. In 2010, scientists in Germany reported using stem cells from bone marrow to treat an 11-month old with HLHS who was in heart failure.  The National Institutes of Health has a great primer on stem cells here.

According to the International Society for Stem Cell Research, “Stem cells are the foundation for every organ and tissue in your body.”  Transplanting stem cells either from the same person (autologous) or from a donor (allogeneic) has been shown to be safe.  However, there are many different kinds of stem cells from all parts of the body that each have different purposes, so scientists first had to do preclinical research to determine which cells would be best to use in regenerating heart muscle.

Researchers found that UCB contains mononuclear stem cells (MNCs), which interact with whatever environment they’re in by releasing cytokines or growth factors.  When put in an environment like the heart, those growth factors act like fertilizer and can stimulate new heart muscle to grow bigger.

Phase I Clinical Trial

Paper - UCB

Decades of research has been done using stem cells to treat heart disease, but almost all of the research has been in adults, not in children or people with congenital heart defects.  The first step in testing any new treatment or drug is to start with a small group of subjects in a Phase I, or pilot study. The goal of a Phase I study is very simple – make sure the new treatment is safe.

Because the heart muscle is more susceptible to regeneration at younger ages, and because autologous MNCs have the lowest rate of complication, researchers on this study decided to collect MNCs from an HLHS-diagnosed baby and inject them into the baby’s own during a planned surgery at three months of age (e.g., the Glenn procedure).

MNCs are also found in bone marrow, but harvesting bone marrow from an infant is challenging and risky.  So researchers decided to collect UCB from the baby at birth and harvest the cells from there.  Because of this novel approach to collecting and processing UCB, this Phase I study also had an additional goal of making sure the entire process was feasible.

There were initial challenges with UCB collection in the early stages of the study.  Collecting UCB is generally done in the delivery or operating room, which is a busy place with many people taking care of the new baby and mother.  Some early collections didn’t have enough cord blood to harvest enough MNCs.  New training was provided to emphasize the importance of collecting as much cord blood as possible, and the collection rates increased significantly.

The first stem cell delivery on this Phase I study was performed in 2015 and our paper reports on the first 10 patients treated at the Children’s Hospital at OU MedicineMayo Clinic, and Children's Hospital of Philadelphia.  A total of 23 patients have now been treated on the trial at additional hospitals in the HLHS Consortium including the Children's Hospital of Los AngelesChildren's Hospital Colorado, and Children's Minnesota.

We are proud to share that the results published in this first paper demonstrate that collecting UCB from an HLHS-diagnosed infant and injecting the MNCs into the heart during the Glenn is both safe and feasible.  There were no operative deaths, and none of the children had any significant safety concerns over the six months after surgery.  According to Dr. Tim Nelson, MD, PhD, Director of the Todd and Karen Wanek Family Program for HLHS at Mayo Clinic:

"The infrastructure is now in place to collect and process stem cells with this method for any HLHS baby born in the United States."

Phase IIb Clinical Trial

The Phase I trial showed that the procedure is safe and feasible.  However, there weren’t enough patients treated to determine its efficacy (e.g., how effective it is).  The promising results suggesting improved growth rates and right ventricular ejection fraction (e.g., the amount of blood being pumped out of the right side of the heart and into the lungs to get oxygen) have led to the development of a Phase IIb trial.  A Phase IIb, or pivotal trial, is designed to evaluate the efficacy of a new procedure by treating more patients.

Paper - MNC delivery

The new study is now open and treating patients at HLHS Consortium hospitals across the country.  It includes both a treatment arm for infants whose UCB has been collected and a control arm for patients diagnosed after birth or who did not collected cord blood for use in the study.

“We’re excited to keep working with the physicians and research teams at these sites, and to continue expanding the consortium with new Centers of Excellence” says Dr. Nelson.  “Individuals with HLHS will have more access to better treatments and groundbreaking clinical trials.”

Read the article on The Journal of Thoracic and Cardiovascular Surgery