Research Snapshot: Study demonstrates protein infusion can restore bone marrow function and rejuvenate the hematopoietic system

By Ian Bennett

A new paper published in Nature Communications demonstrates that the Netrin-1 protein (NTN1) is a key regulator of cells in the bone marrow niche (BM niche) during homeostasis, regeneration and aging. The study is the first to show that infusing NTN1 into the body rejuvenates the BM niche and restores the regenerative capacity of aged hematopoietic stem cells (HSCs). This potential to rejuvenate the regenerative capacity of the body’s blood production system will have immediate therapeutic impact, especially in older patients, the researchers said.

Jason Butler, Ph.D.

The study led by Jason Butler, Ph.D., vice chief of research and a professor in the division of hematology and oncology in the UF College of Medicine, builds on previous work from the Butler lab focused on enhancing the regeneration of the hematopoietic system, or blood system, in the context of myelosuppression, leukemogenesis and aging. Hematopoietic stem cell transplantation therapies are intravenous infusions of stem cells. These infusions have been used to reestablish blood cell production in the bone marrow of patients after hematologic malignancies. However, these treatments can fail and lead to relapses, particularly when older patients receive treatment.

While stem cells in bone marrow are known to play a crucial role in blood cell production, little is known about the mechanisms of stem cells in bone marrow or why older patients have lower activity within the BM niche. Recent research suggested that NTN1 can support some aspects of HSC function, but until now, it was unknown if NTN1 regulated the BM niche or the function of the stem cells within it.

“Up until now, studies on HSC aging have only been able to partially rejuvenate the HSC’s ability to function properly,” Butler said.  “For the first time, this study demonstrates that fully restoring the function of the BM niche requires a rejuvenated hematopoietic system. This is only achievable if the body’s ability to efficiently repair the DNA damage that accumulates during the aging process is restored. We showed that NTN1 is a key part of restoring this ability in the bone marrow niche.”

The results showed that the beneficial effects of NTN1 on the aged hematopoietic system translated into a strong survival benefit and preservation of body weight during serial myelosuppressive chemotherapy. This indicates that infusing NTN1 during recovery from myelosuppression could have a significant therapeutic impact, leading to accelerated recovery and increased survival, according to the researchers. The Butler lab is currently engaged in clinical trials that could improve patient outcomes, underscoring the importance of ongoing research efforts in this field.

“We are excited to begin testing the effects of NTN1 on human BM niche and HSCs. We are hopeful that we can build upon our published study to translate these findings into the clinic,” said Pradeep Ramalingam, M.D., Ph.D., a research assistant professor in the division of hematology/oncology and co-lead author of the study.

Read the study in Nature Communications.

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