Failure of adult marrow-derived stem cells to generate marrow stroma after successful hematopoietic stem cell transplantation

Objective The existence of adult, marrow-derived stem cells that retain the ability to generate various tissues is an appealing concept that has considerable therapeutic potential. The aim of this study was to test the extent of this proposed plasticity by defining the ability of adult marrow and peripheral blood stem cells to generate stromal cells of the marrow microenvironment. Patients and Methods We examined expanded populations of stromal cells from four patients 1 to 27 years after allogeneic, sex-mismatched marrow, or peripheral blood stem cell transplantation. The cultured stromal cells were stained by immunofluorescence and with nonspecific esterase (NSE) to detect macrophages, which can constitute a significant component of a primary long-term marrow culture. Fluorescence in situ hybridization (FISH) probes for chromosomes X and Y were applied to distinguish donor from host cells. Results FISH analysis of replicate slides indicated a good correlation between the number of NSE+ cells and the number of donor-derived cells. By applying NSE and FISH to the same cells and capturing both bright-field and epifluorescence images, we confirmed that all donor signals were derived from NSE+ macrophages. Conclusion After successful allogeneic stem cell transplantation, the marrow stroma remains host in origin, even after 27 years of 100% donor hematopoiesis.