Bone marrow transplantation can be improved by optimizing the dose of transplanted hematopoietic stem cells (HSCs), according to recent results from a mouse model. Bone marrow transplantation is a risky procedure typically used to treat cancer and blood diseases.1
Researchers discovered that transplantation dose affected the behavior of HSCs. HSCs are stem cells that generate blood.
In this study, published in Cancer Reports, researchers marked individual HSCs with a genetic tag to allow the researchers to observe how the HSCs contributed to the formation of blood.
“The dose of transplanted bone marrow has strong and lasting effects on how HSCs specialize and coordinate their behavior,” said Rong Lu, PhD, assistant professor in the Department of Stem Cell Biology and Regenerative Medicine at the University of Southern California, Los Angeles, California, and senior author of the study.
“This suggests that altering transplantation dose could be a tool for improving outcomes for patients: promoting bone marrow engraftment, reducing the risk of infection, and ultimately saving lives.”
While an HSC can act as a generalist to produce all types of specialized blood cells, the researchers noticed that only 20% to 30% of HSCs acted as generalists. These generalist HSCs contributed a balanced lymphocyte production, creating a variety of white blood cells, such as granulocytes, B cells, and T cells. This smaller group of HSCs generated a disproportionately large volume of the blood.
The 70% to 80% of HSCs that remained primarily produced T cells. Researchers discovered that higher doses of transplanted HSCs resulted in more balanced production of types of white blood cells, and lower doses resulted in a bias to T cell production. Higher transplantation doses also differentiated earlier.
“In summary, our data provide a clonal-level perspective on HSC differentiation post transplantation and on its alteration by HSC transplantation dose. These findings offer insights into the complex effects that transplantation dose has on patient survival during bone marrow transplantation,” concluded the authors.
“Patients with different pathogeneses might benefit from distinct differentiation programs associated with particular transplantation doses.”
1. Brewer C, Chu E, Chin M, Lu R. Transplantation dose alters the differentiation program of hematopoietic stem cells [published online May 12, 2016]. Cancer Rep. doi:10.1016/j.celrep.2016.04.061.