New research findings could help improve bone marrow and stem cell transplantation for patients with blood-related diseases

Our analysis will help us improve the bone marrow and stem cell transplant process.

Alejandro B. Balazs, PhD
Ragon Institute of MGH, MIT and Harvard

BOSTON- Hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate into all types of mature blood cells, making them promising treatments for a variety of diseases. However, the mechanisms involved in transplantation – when cells begin to grow and make healthy blood cells after being transplanted into a patient – are poorly understood. A recent study by researchers at Massachusetts General Hospital (MGH) and Boston University School of Medicine revealed the unique signature of genes expressed by HSCs capable of undergoing this process. The resultswhich are published in Nature Communicationcould allow scientists to expand these cells outside the body or convert other types of stem cells into cells capable of repopulating the bloodstream.

In adults, HSCs are found in the bone marrow and bloodstream, but before birth they can be found to a greater extent in the liver, where they multiply or proliferate into other HSCs at a very high rate. raised. Additionally, animal research has shown that HSCs from fetal liver are more capable of engraftment than HSCs from bone marrow.

To understand what enables fetal liver HSCs to have these superior proliferation and engraftment characteristics, researchers examined the gene expression patterns that are unique to these very potent stem cells. They combined this examination with a variety of experimental methods to characterize protein expression and functionality in these same cells.

“This in-depth analysis revealed that these stem cells express a protein on their surface called CD201 which correlates very closely with this grafting potential and can be used to isolate functional stem cells from other cell types,” says the co-author. Principal Alejandro B. Balazs, PhD, Principal Investigator at the Ragon Institute of MGH, MIT, and Harvard. “It will help us improve the bone marrow and stem cell transplant process by allowing us to purify these cells.”

Better understanding of the genes involved will also help scientists propagate HSCs with high transplant potential in the laboratory and manipulate them to more effectively fight blood cell-related diseases such as sickle cell disease, HIV and certain types of cancer. “Overall, this work has resulted in a detailed map of the most potent blood stem cells and will provide insight into why these cells have such extraordinary regenerative capacity. Such knowledge will allow us to create safer and more effective therapies for patients with blood disorders,” says lead author Kim Vanuytsel, PhD, assistant research professor of medicine at Boston University School of Medicine.

Co-lead author George J. Murphy, PhD, associate professor of medicine at Boston University School of Medicine and co-founder of BU and the BMC Center for Regenerative Medicine (CReM), adds that the team’s openly shared resource , which has been made available in an interactive format on https://engraftable-hsc.cells.ucsc.edu, will enable new biological insights into the potential for engraftment and stimulate a wide range of future studies. “This important work would not have been possible without the powerful collegial collaborations that have taken place among institutions in the Boston area. This project is also a shining example of ‘open source biology’ at work, where freely shared information and ideas can be leveraged by all for future discoveries,” he said.

Co-authors include Carlos Villacorta-Martin, Jonathan Lindstrom-Vautrin, Zhe Wang, Wilfredo F. Garcia-Beltran, Vladimir Vrbanac, Dylan Parsons, Evan C. Lam, Taylor M. Matte, Todd W. Dowrey, Sara S. Kumar , Mengze Li, Feiya Wang, Anthony K. Yeung, Gustavo Mostoslavsky, Ruben Dries, Joshua D. Campbell, and Anna C. Belkina.

About Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is Harvard Medical School’s first and largest teaching hospital. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and includes more than 9,500 researchers working in more than 30 institutes, centers and departments. In August 2021, Mass General was named #5 in the US News and World Report list of “America’s Best Hospitals”.

About Boston University School of Medicine
Originally established in 1848 as the New England Female Medical College and incorporated into Boston University in 1873, Boston University School of Medicine (BUSM) is today a leading academic medical center with an enrollment of more than 700 medical students and 1,180 students pursuing graduate degrees in medical sciences. BUSM faculty contribute to over 605 active grants and contracts, with total planned grants valued at over $211 million in the areas of amyloidosis, arthritis, cardiovascular disease, cancer, infectious disease , lung disease and dermatology, among other fields. The school’s teaching affiliates include Boston Medical Center, its main teaching hospital, the Boston VA Healthcare System, Kaiser Permanente in Northern California, as well as Boston HealthNet, a network of 15 community health centers . For more information, please visit http://www.bumc.bu.edu/busm/

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