University of Minnesota stem cell researchers, together with collaborators at Stanford University, have successfully used adult stem cells to replace the immune system and bone marrow of mice, offering the promise of new therapies for people in the future. With this advance and other recent discoveries, the researchers are winning over previous skeptics.
For decades, researchers have tried in the lab to expand hematopoietic stem cells (cells that give rise to the blood system). Success in this venture would mean increasing the supply of cells available for bone marrow transplant patients. The researchers used multipotent adult progenitor cells (MAPCs), which can be isolated from bone marrow and have the ability in the laboratory to differentiate into different specific types of cells such as liver, bone and neural cells.
Catherine Verfaillie, M.D., director of the University’s Stem Cell Institute, first identified MAPCs in 2001. Since then, many in the scientific community have been skeptical of their existence and their functioning as Verfaillie has described. This skepticism mostly arose due to difficulty in reliably growing these cells, which made reproduction in other labs problematic. Since their identification, the methods to isolate and grow MAPCs have been improved (see publication in Experimental Hematology, October 2006). This latest research will be available online from the Journal of Experimental Medicine on January 15; it will appear in the Jan. 22, 2007; print edition of the journal.
Verfaillie and her team isolated MAPCs from mice and expanded them for at least 80 doublings in the lab. They then transplanted the cells into mice that received radiation and thus had no immune system.
"The cells not only survived when transplanted but they completely repopulated the blood system of the mice," Verfaillie said. The MAPCs did not differentiate into other cell types, such as liver or brain cells, nor did they form tumors in any animals.
Irving Weissman, M.D., Stanford University professor of pathology and developmental biology and co-author on the manuscript, was admittedly skeptical at first about the ability of MAPCs to contribute to blood formation. This skepticism made him an ideal collaborator, as he insisted on rigorous evaluation of the data. "These experiments point to potential precursors of blood forming stem cells in an unexpected population of cultured cells," said Weissman, who directs Stanford’s Institute for Stem Cell Biology and Regenerative Medicine.
"Scientists must now understand that mouse MAPCs can make normal blood, and we need to explore how they do it," Weissman said. "It is very important to note that MAPCs were not themselves radioprotective, thus they alone could not be used in patients in whom the bone marrow is totally eliminated due to radiation or chemotherapy, but it is still remarkable that they can give rise to blood cells."
Bruce Blazar, M.D., professor of Pediatrics at the University of Minnesota, who is co-author of the paper, has continued with experiments conducted in his laboratory after the completion of this study. "Our results independently confirmed in an additional series of animals the finding that MAPCs can make blood cells," Blazar said. While more research will need to be done and studies need to be replicated with human MAPCs before human treatments are available, this research suggests that MAPCs could be used to help reduce rejection of tissue transplants. In the future, physicians may be able to introduce MAPCs in the blood system of the recipient to trick the immune system into accepting the MAPC-generated transplanted tissue. In addition to this paper, in the last few months further evidence of MAPCs existence and function was published in scientific peer-reviewed journals based on research done at the University and other research institutions across the world. "I am pleased to see this science replicated at other research universities," Verfaillie said. "Now there is further confirmation that the MAPCs could be a valid source of new therapies." Verfaillie added this research shows the importance of continuing to pursue all types of stem cell research, adult and embryonic, because scientists do not yet know which cell type will prove most promising for treating a particular disease.
