More than 1,000 infants were randomly assigned either to umbilical cord milking or delayed cord clamping. Rates of severe intraventricular hemorrhage (bleeding inside the brain) and/or death did not differ significantly between the two groups (just over 1%). Moreover, the rates of overall intraventricular hemorrhage were also similar between the groups (approximately 12%). The researchers will follow all the infants in the study for two years to observe longer term outcomes.
A team led by researchers from Department of Hematology and Department of Molecular Pathology, Singapore General Hospital (SGH) have developed a platform to harness and enhance the innate ability of white blood cells from umbilical cord blood to treat various types of solid and blood cancers. The platform performed well in pre-clinical studies and will be put to further test in a phase 1 clinical trial as early as 2024 for leukemia and lymphoma treatment.
The white blood cells, known as gamma delta T-cells (GDT), have antiviral and antitumor properties. These cells keep a look out for signs of biological stress like cancerous or infected cells in the body and are one of the first lines of defense against disease.
The idea was to create a fairly universal treatment, rather than chasing individual therapies for all of these rare diseases, and to do so with minimal risk to the patients. The results were published in today’s print edition of Blood Advances.
“There has been a lot of emphasis placed on cool new technologies that might address these diseases, but—even if they prove effective—those aren’t available to most centers,” said study senior author Paul Szabolcs, M.D., division director of bone marrow transplantation and cellular therapies at UPMC Children’s Hospital. “The regimen we developed is more robust, readily applicable and will remain significantly less expensive.”
For this study, the participants received intravenous injections of banked cord blood, which was donated from the umbilical cords and placentas of healthy babies just after birth and frozen until needed.
To make room in their bone marrow for donor stem cells to take root and prevent them from being rejected, study participants received a low dose of chemotherapy and immunosuppressant drugs in a careful sequence. Once the cells integrated into the patients’ bodies, these drugs were tapered off. To kick the immune system back into gear, the researchers reserved a small fraction of the cord blood and gave it to participants a few weeks after the initial infusion.
It’s important to note that this procedure doesn’t require the donor and recipient to have matching immune profiles.
“That’s huge for ethnic minorities,” Szabolcs said. “The probability of a perfect match is very low, but with a cord blood graft, we have a chance to overcome this discrepancy over the course of a couple months and then taper immunosuppressants away.”
A molecule of hope
Recently, a new molecule called UM171, discovered by Dr. Guy Sauvageau and his colleagues at Université de Montréal, made it possible to increase up to 30 times the number of stem cells in umbilical cord blood in the laboratory, and showed promising results in 22 patients primarily suffering from leukemia. In the study, which will be conducted on a cohort of 10 multiple myeloma patients at high risk of relapse, umbilical cord blood will be grown in a laboratory using the UM171 molecule, then injected in patients in the hope of treating the disease with fewer immune system complications. If the predicted results are confirmed, allografting umbilical cord blood, made possible thanks to the UM171 molecule, could become the preferred treatment for patients with multiple myeloma.
The data set, one of the largest of its kind, includes primary data and associated metadata from nearly 530,000 immune cells from umbilical cord blood of newborns and bone marrow of adults. Additional data sets were also provided by Wellcome Sanger Institute and collaborators.
“This is a wonderful example of science at its most open and collaborative,” said team co-leader Orit Rozenblatt-Rosen, an Institute Scientist at the Broad and director of the Klarman Cell Observatory (KCO).
This data lays the foundation for an immune cell atlas, an important first step in the Human Cell Atlas consortium’s goal of an initial draft atlas of 30 million cells covering many tissues. “The immune system is deeply complex, involved in many diseases, and distributed throughout our body. This data set will be critical to help unlock its secrets,” said Monika Kowalczyk, a hematologist who led the experimental team while a postdoctoral researcher in the lab of Broad Core Institute Member Aviv Regev.
By making the data openly accessible before drafting their manuscript for publication the researchers have provided the broader scientific community with a valuable resource. The data set can reveal basic biology, provide a reference for studying disease, and allow computational biologists to test new analysis tools on a large data set that would be hard for smaller labs to generate.
“Collecting and processing half a million immune cells was a Herculean feat, involving tightly coordinated teamwork across many areas of expertise,” said team member Danielle Dionne of the KCO at the Broad.
First, Kowalczyk and her KCO colleagues Dionne, Michal Slyper, and Julia Waldman isolated single cells from human cord blood and bone marrow samples and prepared them for sequencing. This required meticulous advanced planning since the team was handling 224,000 cells from four patients in a 20-minute window—up to 100-fold more cells than in a typical experiment.