Umbilical cord blood: a lifeline for pediatric diseases

Caridad Martinez has a bone to pick with bone marrow. In 2008, during her pediatric bone marrow transplant fellowship, Martinez met newborns with severe immunodeficiencies. Those patients’ bone marrow manufactured dysfunctional blood and immune cells. The kids were dying. The standard remedy was to fetch marrow from a donor to hopefully replace the faulty cells with healthier ones.

Being in a place where there are so many minorities who didn't have a marrow donor … it was very important to explore the options of using a cord transplant for these diseases.
– Caridad Martinez, Baylor College of Medicine and Texas Children’s Hospital

However, finding a bone marrow match can be hard, especially for racial and ethnic minorities. “You don't have the same representation of donors,” said Martinez, who is now a bone marrow transplantation researcher at Baylor College of Medicine and a physician at Texas Children’s Hospital. White patients have a 79 percent chance of finding an unrelated donor; Black and African American patients have just a 29 percent chance (1). At the time of Martinez’s fellowship, marrow transplants were a stalwart in the field, but she noticed an urgent need to challenge the status quo. She found that opportunity with a then-budding type of transplant that she felt might be more accessible: transplanting blood from umbilical cords.

Cord blood is rich in stem cells and other potentially regenerative compounds, so researchers believe that it should be well suited for melding into a new environment and regenerating the recipient’s tissues. Animal studies also suggest that the contents of umbilical cord blood could treat cancer, retinal problems, and neurological disorders like Parkinson’s disease (2,3). A newborn’s cord blood is also less likely to attack the recipient’s cells since it contains fewer mature immune cells. That lowers the risk of graft-versus-host disease and widens the window of available donors. “They don't attack as much,” Martinez said. “You don't need to match at the same degree.”

Martinez learned the ropes of cord blood transplants and got hired to build a program offering the treatment at Texas Children’s Hospital. She estimates that about 60 percent of her patients there are racial minorities. “Being in a place where there are so many minorities who didn't have a marrow donor,” said Martinez, “it was very important to explore the options of using a cord transplant for these diseases.”

Groundbreaking clinical trials over the past decade are finally bringing evidence to light to support cord blood’s role in treating pediatric disease even beyond immune and blood disorders. The surge of new evidence has doctors excited that, thanks to cord blood, many kids may live far longer than their parents expected.

Heal yourself

Much of cord blood’s therapeutic power comes from its cocktail of regenerative components: stem cells, growth factors, and inflammatory cytokines. An extra advantage materializes in applications where a patient can use his or her own cord blood. These autologous transplants intrinsically skirt around rejection risk.

“It's genetically identical to the patient who will be treated,” said Tim Nelson, a physician scientist at the Mayo Clinic. For over a decade, Nelson’s team has investigated cord blood as a treatment for hypoplastic left heart syndrome (HLHS), in which babies have malformed hearts.

HLHS begins months before a newborn sees the light of day. The fetus’ heart develops in such a way that it is essentially missing its entire left side. A series of three invasive surgeries — one at three days old, one at three months, and one at three years — replumbs the heart to pump with a single chamber. “It’s the best we can do,” Nelson said. “But it's not a cure.”

Tim Nelson wears a lab coat, gloves, and goggles while pipetting in his research laboratory.

Tim Nelson’s team at the Mayo Clinic evaluates whether cord blood could help treat hypoplastic left heart syndrome.

Credit: Mayo Clinic

The surgeries leave babies with a “grossly inadequate” heart that Nelson likens to a five-horsepower engine. The heart remains too weak to handle the blood flow that the body expects it to handle. About half of the kids born with HLHS don't make it to their fifth birthdays.

Nelson’s team hopes to augment the three-staged surgery with injections of cells from that child’s own cord blood, essentially fertilizing the hearts of patients with HLHS. After being injected into the heart muscle, the new cells set off a cascade of regrowth. Cytokines and growth factors stimulate the heart muscle to divide into new heart muscle cells, helping the body heal itself.

“Imagine if we can, through regenerative sciences, convert a five-horsepower engine into a 50-horsepower engine,” he said.

A Phase 1 clinical trial began about a decade ago to test the feasibility of collecting enough cord blood and the safety of treating infants with it (4). In that trial, the researchers’ scheme to collect, process, and deliver cord blood worked 80 percent of the time. (Some newborns had too little cord blood.) And each of the 10 children treated survived.

The team published their findings in 2019 and have since continued with a Phase 2 study (5). Newborns received the traditional first surgery at three days of age. Then during the second surgery at three months, doctors injected cells into the children’s heart muscles. The most recent wave of participants also received injections during the third surgery, at three years old. “93 patients now have been treated with some form of the cells, and we haven't seen any adverse events that have caused a safety concern or would cause us to discontinue the trials,” Nelson said.

It’s still too early to tell just how effective the regrowth treatment is, so Nelson is pleased but cautiously optimistic. He recognizes how instrumental cord blood has been to start clinical testing for important cell therapies that may one day heal infants with congenital heart disease. Cord blood “was the place where the field was launched, and it's the place that will launch us into many additional things as we go forward,” he said.

New blood

Doctors use cord blood to regenerate tissue throughout the body too. At Texas Children’s Hospital, Martinez’s team focuses on nonmalignant pediatric disease — conditions such as immune deficiencies, rather than cancers. Timing is key for congenital immunodeficiencies because the children are in fragile conditions; doctors can get cord blood transplants ready in less than two weeks, compared to at least six to eight weeks for bone marrow.

Caridad Martinez wears a white lab coat and smiles in a portrait.

Caridad Martinez’s team at Texas Children’s Hospital uses umbilical cord blood transplants to treat immune disorders in newborns.

Credit: Baylor College of Medicine

Doctors typically treat these diseases with a graft of donor blood and immune cells, usually from a bone marrow or cord blood match, but the graft can’t take hold on its own. Patients must go through a conditioning regimen where they receive chemotherapy or radiotherapy to treat the disease and then antibody treatment to eradicate the existing immune system.

This process sets the patient up to accept a graft, but there’s a catch. Antibody treatments linger after the graft and kill new donor immune cells too, which delays the immune system’s regrowth.

“If those stem cells take a long time to grow, then the patients are more prone to have infections,” Martinez said. Cord blood’s edge therefore comes from what it doesn’t contain.

When adults donate tissue, like bone marrow, they inevitably donate viruses they’ve encountered in life as well. Though latent in the donor, these viruses risk starting new infections in the recipient. “But when you use an umbilical cord as the stem cell source, those are babies,” said Martinez. “They have basically never seen anything out in the world. You can't get any younger than that.” That means that cord blood brings less infection and rejection risk.

In a clinical trial that began over a decade ago, Martinez’s team hypothesized that cord blood could let them skip the antibody treatment and replace it with a shorter-lived chemotherapy (6). They figured that the chemotherapy would wipe out the dysfunctional immune system, then vanish in time for the new cells to do their thing.

The infants enrolled in the trial spanned in age from one month old to almost 10 years, with a median age of about five months. The patients spent four to six weeks in the hospital preparing for the transplant, receiving it, and getting monitored afterward.

So far, the results confirm what Martinez hoped. The grafted cells from cord blood replenish the kids’ immune systems noticeably quicker. “Donor cells are growing very early,” she said. Normally after a transplant from other donor sources, it takes about 18 to 24 months for children’s immune systems to regenerate enough for them to safely get their vaccines. The cord blood patients started receiving vaccines around nine months after the transplant.

When you have a family that has lost a baby before and they want to do this and have an opportunity to have a healthy kid … it's a priceless experience. It's very hard to put into words what that means.
– Caridad Martinez, Baylor College of Medicine and Texas Children’s Hospital

None of her patients have rejected the grafts, and none died of secondary infections. “We have patients who are in their 20s, and they still come and see us once a year,” Martinez said. The team recently published these findings (7).

“When you have a family that has lost a baby before and they want to do this and have an opportunity to have a healthy kid,” she said, “it's a priceless experience. It's very hard to put into words what that means.”

Cord blood banking is on a steady rise: The US registry contains 9 million donors (8,9). Martinez hopes that the number continues to rise and points to her recent results as a testament to the invaluable impact cord blood transplants have had on her community thus far. She estimates that 80 percent of patients who come to her hospital don’t have a bone marrow match. Umbilical cord blood transplants are now the standard treatment for those kids.

“When I see patients who are 14 and were one of my first babies, and I see them going to school, telling me their career goals, and fishing — doing all kinds of things, it’s touching,” Martinez said. “I feel that my purpose has been accomplished.”