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Stem Cell Study Offers Clues for Optimizing Bone Marrow Transplants and More

LOS ANGELES, CA (US), January 2019 — Bone marrow transplants, which involve transplanting healthy blood stem cells into patients, offer the best treatment for many types of cancers, blood disorders and immune diseases. Even though 22,000 of these procedures are performed each year in the United States alone, much remains to be understood about how they work.

A new study by researchers at the University of Southern California and Stanford University deepens the mystery. It shows that successfully transplanted stem cells don't behave "normally," as in a healthy recipient without a transplant. Instead, the radiation and high-dose chemotherapy used to wipe out diseased stem cells prior to transplantation appear to trigger "extreme behavior" in the newly transplanted cells.

The findings appeared in Proceedings of the National Academy of the Sciences (PNAS) on Jan. 8.

"Our research has important implications for understanding and optimizing bone marrow transplants and certain types of gene therapy," said lead researcher and co-corresponding author Rong Lu, assistant professor of stem cell biology and regenerative medicine at USC. The other co-corresponding author is Irving Weissman, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

In a series of experiments, scientists learned that when transplanted into an irradiated mouse, only a very small minority of the stem cells produce blood and immune cells, while many other stem cells become dormant and do nothing. In addition, post-radiation, this handful of "super producer" stem cells also become biased towards producing only certain types of immune cells. However, the overall blood and immune system still tends to remain balanced.

In mice that had not undergone radiation, all stem cells contributed equally to the blood and immune systems, with the exception of T cells, suggesting that the preconditioning regimen used to ensure successful transplantation is the source of the abnormal cell behavior.


After radiation, a small number of blood stem cells make an outsized contribution to reconstituting the blood and immune system. Image courtesy of Jiya Eerdeng/Rong Lu Lab.

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DOI: 10.1073/pnas.1801480116