INDIANAPOLIS — Scientists at the Indiana University School of Medicine have identified an unforeseen way lung cells can help keep blood stem cells healthy. The discovery, recently published in Molecular Therapy, presents opportunities for new therapies to strengthen stem cell health and improve treatments for bone marrow failure and serious blood diseases like sickle cell disease.
Hematopoietic stem cells, or blood stem cells, live primarily in the bone marrow and are responsible for producing all types of mature blood cells throughout a person’s life. Blood stem cells have the ability to renew themselves, making them especially valuable in treatments like stem cell transplants for patients with weakened or damaged blood systems.
Traditionally, hematopoietic stem cells were believed to be supported only by their local bone marrow environment. The new study is the first to suggest that human lung cells can also help strengthen blood stem cell performance. This is accomplished through a unique process involving exosomes, the tiny, membrane-bound packages that carry proteins, ribonucleic acid (RNA) and other molecules between cells.
“We found that these lung-derived exosomes specifically interact with long-term hematopoietic stem cells and enhance their ability to self-renew and maintain their ‘stemness,’” said Reza Shahbazi, PhD, assistant professor of medicine at the IU School of Medicine and the study’s lead author. “This is critically important because in many diseases, or after chemotherapy, hematopoietic stem cells’ performance can decline, leading to anemia and other blood-related complications.”
Using a new exosome labeling and identification method, the researchers tracked exactly how these exosomes interacted with blood stem cells and identified specific microRNAs that act like “on switches” for stem cell repair. In animal models, treating injured bone marrow with these exosomes led to faster and more complete recovery of healthy blood cells.
“In conditions like bone marrow failure and sickle cell disease, blood stem cells are essential for patient recovery, but often lack the strength for successful transplants,” said Reuben Kapur, PhD, director and program leader of the Hematologic Malignancies and Stem Cell Biology Program at the Herman B Wells Center for Pediatric Research and co-author of the study. “Our findings suggest that lung-derived exosomes, or the key molecules they carry, could be developed into a therapy to accelerate this recovery process, helping reduce complication rates and improve survival. Most importantly, this therapy could be used alongside standard transplantation methods to make the entire process safer and more effective.”
Left to right: Sanam Rezaei Benam, Reza Shahbazi, Xuepeng Wang and Reuben Kapur. | Photo by Tim Yates, IU School of Medicine
This collaborative study involved scientists from the Wells Center, the IU Melvin and Bren Simon Comprehensive Cancer Center and the cancer center's Brown Center for Immunotherapy. Future research will focus on pinpointing the most important microRNAs in these exosomes, testing their safety and validating results in larger pre-clinical models.
“We want to explore whether we can make synthetic versions of these exosomes for consistent, large-scale production,” said Xuepeng Wang, PhD, assistant research professor of pediatrics and co-author of the study. “Ultimately, these studies will help determine if this strategy is ready to be tested in early-phase clinical trials for patients.”
Additional IU co-authors of the study include Sanam Rezaei Benam and Samaneh Maleknia.
This research was supported by funding from the National Institutes of Health, the American Society of Gene and Cell Therapy and the Cystic Fibrosis Foundation.
About the Indiana University School of Medicine
The IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability. According to the Blue Ridge Institute for Medical Research, the IU School of Medicine ranks No. 13 in 2024 National Institutes of Health funding among all public medical schools in the country.
Writer: Jackie Maupin, jacmaup@iu.edu
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