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Mapping the Elusive MAPC: Questions settled about a powerful stem cell
By Chris Scott*
Prompted by an unexpected observation that cells coming from the bone marrow take on the appearance and gene expression pattern of neural cells, the University of Minnesota's Catherine Verfaillie set out to determine whether the culprit was the hematopoietic stem cell (HSC) or mesenchymal stem cell. The answer was neither.
In 2002 the Minnesota group isolated a stem cell from the marrow, brains and muscles of mice, and named them multipotent adult progenitor cells (or MAPCs). (REF 1) In the lab, MAPCs grow indefinitely and express telomerase, the enzyme associated with cellular immortality. They appear to change into liver cells, neurons and even HSCs themselves. A MAPC passes an important developmental test: put one into a mouse embryo and it integrates seamlessly into most parts of a baby mouse.
One criticism of the early experiments is that other labs found it difficult to repeat the results- the cells are very finicky. And, the team hadn’t conclusively shown that MAPCs regenerate tissue in an animal. Did the MAPCs actually exist in vivo, or were they just an interesting laboratory artifact?
A paper published in January by Verfaillie helps to settle these questions. (REF 2) The experiment carefully monitored the fate of MAPCs in animals. To make the cells easy to follow, the group genetically marked MAPCs with a green florescent protein. A stem cell so marked will change, or differentiate, into more mature types of cells, which will also be green. The team irradiated mice to eliminate the stem cells in the bone marrow, which produce all blood cells, and injected the MAPCs. The MAPCs could replace all cells in the blood and bone marrow, and fully reconstitute the immune system of the irradiated mouse.
Will MAPCs substitute for embryonic stem cells? Though they can divide endlessly and change into several cell types, MAPCs grow much slower than embryonic stem cells. They are also rare. Estimates are that less than 2,000 exist in an adult mouse. But, these cells appear to carry at least one advantage over embryonic stem cells: they don't form tumors when transplanted.
The bottom line: Future therapies may spring from many kinds of stem cells, including the elusive and powerful MAPC.
REF 1: Yuehua Jiang, et al. "Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain." Experimental Hematology, 30 (2002): 896-904
REF 2: Marta Serafini, et al. "Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells." The Journal of Experimental Medicine, Published online 16 January 2007 doi:10.1084/jem.20061115
Notes
Jiang, Y., Vaessen, B., Lenvik, T., Blackstad, M., Reyes, M., and Verfaillie, C. M. (2002). Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol 30, 896-904.
Serafini, M., Dylla, S. J., Oki, M., Heremans, Y., Tolar, J., Jiang, Y., Buckley, S. M., Pelacho, B., Burns, T. C., Frommer, S., et al. (2007). Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells. J Exp Med 204, 129-139.
*Author affiliation
Christopher Scott
Stanford Program on Stem Cells in Society, Stanford University
Author of Stem Cell Now
Posted
April 6, 2007
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