UF Health Cancer Institute researchers have pinpointed the cellular source of a protein that decreases the function of blood stem cells as people age.
The findings, presented at the American Society of Hematology 67th Annual Meeting and Exposition in Orlando on Sunday, give researchers a target for developing a new treatment to restore the health of blood stem cells and improve recovery from cancer treatments.
“We found that when you’re excluding this protein from the equation in mouse models, you end up with more robust and faster blood count recovery,” said lead author Arianna Smith, a graduate student in the lab of UF Health Cancer Institute member Jason Butler, Ph.D. “Although you’re hitting these mice with strong doses of chemotherapy, they’re able to respond a lot faster, especially for important clinical markers like white blood cell counts.”
As people age, blood stem cells in the bone marrow gradually lose function, often leading to immune system complications and weakened responses to chemotherapy. Past research by the Butler lab has found that eliminating the protein, called thrombospondin-1, improved the health of blood stem cells. When stem cells without the protein were transplanted into mice, the stem cells behaved like young stem cells and engrafted well.
In the new study, Smith set out to find the cellular source of thrombospondin-1. She also wanted to determine how eliminating the protein affected recovery after cancer treatments such as blood marrow transplantation, chemotherapy and radiation. After testing in many different cell types, she found that endothelial cells are the main source of the protein.
“Endothelial cells producing this protein are the primary driver of the decline in function of stem cells throughout the aging process,” she said. “They’re also the primary source of recovery after treatments that suppress the blood system. We now have something to target.”
Older adults are not only more susceptible to cancers, but traditional cancer treatments are harder on their bodies. They often take longer to recover and have more complications.
“Finding ways to protect people’s blood systems while giving them cancer therapies is critical,” said Butler, a professor and vice chief of research in the UF Division of Hematology and Oncology. “Being able to rejuvenate blood stem cells and the environment where they live has a lot of therapeutic potential.”
The research team is now developing antibodies to the protein and moving toward testing potential therapeutics in human blood stem cells.
UF Health Cancer Institute member Pradeep Ramalingam, M.D., Ph.D., and laboratory manager Cody Carter were co-authors on the study.
