However, even when the researchers accounted for risk factors that might affect the gut flora, they found that the link between future diagnosis remained for many of the bacteria. This indicates that some of the differences in gut flora between children with and without future diagnosis are not explained by such risk factors.
The research is at an early stage and more studies are needed, but the discovery that many biomarkers for future developmental neurological disorders can be observed at an early age opens up the possibility of developing screening protocols and preventive measures in the long term.
A method that enhances the functionality of an often-overlooked type of stem cell could lead to better treatments for blood-related diseases, according to new research.
“These cells could go a long way toward improving regenerative medicine,” says Jasmeen Merzaban, a biochemist at KAUST who led the research.
In stem cell transplants—also referred to as bone marrow transplants—patients with malfunctioning bone marrow are infused with a new set of healthy blood-forming stem cells, known as hematopoietic stem cells (HSCs).
These cells have historically been identified by the presence of a protein called CD34. HSCs that express this surface marker are celebrated for their proficiency in homing to and establishing themselves within the bone marrow.
However, this emphasis on CD34-positive HSCs has inadvertently sidelined a population of CD34-negative counterparts, cells mostly found in umbilical cord blood that—although limited in their migration abilities within the bloodstream—are thought to have greater regenerative capacity because of their more primitive developmental state.
The study is the first to use stem cells as part of primary surgery to repair cleft palate in an infant. Dr. Botero and colleagues note that their patient will need further monitoring to ensure adequate bone thickness in the upper jaw. The researchers emphasize the need for further studies evaluating their stem cell technique in a large number of patients—including steps to confirm that bone formation results from the stem cells, and not from the initial “boneless bone graft” surgery.
“Life-saving bone marrow transplants have been the common practice for decades, but this doesn’t work for everybody,” says Stowers Institute Investigator Linheng Li, Ph.D., study lead who is also co-leader of the cancer biology program at the University of Kansas Cancer Center and an affiliate professor of pathology and laboratory medicine at the University of Kansas School of Medicine.
Only 30 percent of patients have a bone marrow donor match available in their families, according to the US Department of Health and Human Services. More than 170,000 people in the US are expected to be diagnosed in 2018 with a blood cancer (leukemia, lymphoma, or myeloma) according to the American Cancer Society.
Adult stem cells from umbilical cords are more likely to be a match for more people because there are fewer compatibility requirements than for a bone marrow transplant. But adult patients need two cords’ worth of blood per treatment, and there aren’t enough cord units available for everyone who needs the treatment. “If we can expand cord adult stem cells, that could potentially decrease the number of cords needed per treatment. That’s a huge advantage,” says Li.
In the study, published online July 31, 2018, in Cell Research, researchers zeroed in on a protein that affects multiple targets and pathways involved in hematopoietic stem cell self-renewal, a broader approach than other studies that focus on a single target or pathway in the process. The protein, called Ythdf2, recognizes a particular type of modification on a group of mRNAs encoding key transcription factors for hematopoietic stem cell self-renewal and promotes the decay of these mRNAs within cells.
When the team knocked out Ythdf2 function in a mouse model or knocked down Ythdf2 function in hUCB cells, they observed increased expression of these transcription factors and expansion of hematopoietic stem cells, which are the major type of adult stem cells in hUCB. They observed that impairing Ythdf2 function did not alter the types of cells that were subsequently produced, nor did it lead to increased blood cell malignancies. In addition, the knock down treatment isn’t permanent, thereby allowing Ythdf2’s function to be restored after transplantation.
“Our approach of targeting Ythdf2 function using an RNA-based technique also helped avoid more persistent DNA-related changes such as mutations in epigenetic regulators,” says Zhenrui Li, Ph.D., a predoctoral researcher at the University of Kansas Medical Center who is performing thesis research in the Linheng Li Lab and first author of the study.
Those kinds of genetic mutations could lead to the re-genesis of leukemia or cancer, Zhenrui Li explains. Since the Ythdf2 protein is present in different kinds of adult stem cells, targeting it and how it affects hematopoietic stem cells seemed a safer approach and, if it worked, broadly applicable.