The proposed existence of adult, marrow derived stem cells that have retained the potential to generate muscle, liver, neurons, etc., is conceptually appealing. However the current data in support of this concept are more intriguing than compelling. To contribute to the resolution of this uncertainty we propose to investigate the contribution of donor marrow stem cells to skin, gut epithelium, liver, muscle, and marrow stroma. We hypothesize that if """"""""plastic stem cells"""""""" originate or reside in marrow they will, with time and/or challenge, contribute to nonhematopoietic tissue regeneration. To test this hypothesis we propose to analyze tissue from patients who are long term survivors of sex mismatched allogeneic marrow transplantation. Currently there are more than 2,300 patients from 1 to 25 years post transplant, who are being actively followed for late complications by the Long Term Follow UP (LTFU) program of the Fred Hutchinson Cancer Research Center. These complications affect all organ systems including skin, eyes, GI tract, liver, lungs, muscles, connective tissue, bladder, kidneys, and central nervous system. Through the efforts of the LTFU office an aliquot of tissue biopsies obtained for diagnostic purposes will be made available for studies proposed here. Tissue samples from these patients will be evaluated in two ways: first, by standard fluorescence in situ hybridization (FISH) for detection of sex chromatin in histological sections; second, by ex vivo expansion of defined cell populations followed by FISH as well as polymerase chain reaction (pcr) amplification of donor versus host DNA. These strategies should improve the signal to noise ratio and make the detection of donor derived cells more reliable. The information gained should help define whether, and under what circumstances, marrow derived stem cells contribute to other tissues following allogeneic transplantation.
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| Shi, Daqing; Reinecke, Hans; Murry, Charles E et al. (2004) Myogenic fusion of human bone marrow stromal cells, but not hematopoietic cells. Blood 104:290-4 |
| Awaya, Norihiro; Rupert, Kathleen; Bryant, Eileen et al. (2002) Failure of adult marrow-derived stem cells to generate marrow stroma after successful hematopoietic stem cell transplantation. Exp Hematol 30:937-42 |
