Human marrow-derived mesenchymal stem cell (MSC) can be differentiated into multiple mesenchymal cell lineages such as bone, cartilage, tendon, muscle, adipose tissue, and marrow stroma. Horwitz et al. (1999) reported that 1-2.5% of donor mesenchymal cells were found in the host bone marrow of osteogenesis imperfecta children patients after allogenic bone marrow transplantation. Osteoporosis also emerged as a major cause of mortality in severe thalassemic children patients due to the over expansion of erythroid lineage and involvement of bone formation supression. However, osteoporosis in severe thalassemic patients is absent following stem cell transplantation. The objective of this study was to define the origin of marrow-derived MSCs in severe thalassemic patients in post stem cell transplantation. MSCs from the bone marrow of 4 severe thalassemic children patients in post stem cell transplantations were cultured and expanded in vitro to define their origin by short tandem repeat (STR) polymorphism and fluorescence in situ hybridization(FISH) analyses. Phenotypic analysis of mesenchymal stem cell was studied by flow cytometry. Phenotypic analysis by flow cytometry revealed that the culture-expanded MSCs were negative for the expression of CD14, CD34, CD45, CD41, and HLA-DR. STR analysis was performed in MSCs from 3 patients with sex-matched donors. The results showed host origin. FISH was performed for detection of XY chromosome in one female patient with a sex-mismatched donor. There was 0.79% donor MSCs showed XY chromosomes while the base line cut off of the XY probe was 2.6%. This data suggests that the MSCs were host origin, and donor MSCs could not engraft in bone marrow of severe thalassemic patients following stem cell transplantation.