Researchers used new blood forming stem cells to replace the immune systems of mice.
Creating a new immune system for people with genetic or autoimmune blood diseases by transplanting adult stem cells is the eventual goal that researchers at the Stanford University School of Medicine have taken a small but significant step towards in their mouse studies.
Effectively replacing their immune systems, the scientists found a way to transplant new blood-forming stem cells into the bone marrow of mice.
Irving Weissman, MD, a co-senior author of the study and director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine said that many aspects of the technique would need to be adapted prior to human testing.
Weissman suggested the remaining hurdles could eventually be overcome, which include the type of mice that was used which were a poor mimic of the human immune system.
The benefits have great potential when those barriers are overcome.
A person’s immune cells attacks their own body when they are afflicted with an autoimmune disease such as multiple sclerosis. Their defective immune system could potentially be replaced with an entirely new immune system that would not attack the body; an immune system transplant, live a heart or liver transplant, could be performed in order to accomplish this.
All the cells of the blood are generated by blood forming stem cells in the bone marrow. A new immune system can be created by transplanting new blood-forming cells into the bone marrow, but the defective cells must be eliminated first. Radiation or intensive chemotherapy is the typical method used to wipe out the existing system. However, increased risk of cancer, brain damage, infertility, and other tissue damage can be caused by chemotherapy while it eliminates the cells of the bone marrow. This makes the therapy inadequate, since the exchange of brain function in order to rid one’s self of multiple sclerosis is not a fair trade.
One potential path around the problem would be to eliminate only the blood-forming stem cells without affecting bone marrow cells or other tissues thought Weissman and co-first author Deepta Bhattacharya, PhD, a postdoctoral scholar in Weissman’s lab. The cells can be effectively destroyed by injecting mice with molecules that latch on to specific proteins on the surface of the blood-forming stem cells. This feat was accomplished by the team which included Agnieszka Czechowicz, first author and medical student. Without further harming the mice, the technique eliminated the blood-forming stem cells.
“It is essentially a surgical strike against the blood-forming stem cells,” said Weissman, the Virginia & D.K. Ludwig Professor for Clinical Investigation in Cancer Research.
A new blood and immune system was established after the transplanted new blood-forming stem cells took residence in the bone marrow.
The new immune system would no longer attack tissues of the body in the person with autoimmune disease. For example, eliminating the cause of the disease in people with a genetic disorder such as sickle cell anemia, the new blood system would not have the sickle-cell mutation. But the hurdles that stand in the way are tall.
First, the researchers don’t know whether the same molecule on human blood-forming stem cells would be the right one to target with a therapy. Additionally, a functioning immune system is missing in the mice involved in the study. Before tests can begin on humans, the technique must first be tested on mice with normal immune systems.
Weissman said he considered this work to be the beginning of research that could lead to human studies although the steps will take time to overcome.
The November 23rd issue of Science published the study.
Also contributing to the work was postdoctoral scholar, Daniel Kraft, MD.
The National Institutes of Health, the Cancer Research Institute, and the Stanford Medical Scholars Program provided fellowships to fund the research.