Human mesenchymal stem cells are not of donor origin in patients with severe aplastic anemia who underwent sex-mismatched allogeneic bone marrow transplant
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Human mesenchymal stem cells are not of donor origin in patients with severe aplastic anemia who underwent sex-mismatched allogeneic bone marrow transplant. / Stute, Norbert; Fehse, Boris; Schröder, Jens; Arps, Sönke; Adamietz, Peter; Held, Karsten R; Zander, Axel R.
In: J HEMATOTH STEM CELL, Vol. 11, No. 6, 12.2002, p. 977-984.Research output: SCORING: Contribution to journal › Short publication › Research › peer-review
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T1 - Human mesenchymal stem cells are not of donor origin in patients with severe aplastic anemia who underwent sex-mismatched allogeneic bone marrow transplant
AU - Stute, Norbert
AU - Fehse, Boris
AU - Schröder, Jens
AU - Arps, Sönke
AU - Adamietz, Peter
AU - Held, Karsten R
AU - Zander, Axel R
PY - 2002/12
Y1 - 2002/12
N2 - Stromal defects are part of the etiology of severe aplastic anemia (SAA), and hematopoietic engraftment is poor in unrelated and mismatched transplant. Therefore, we wanted to find out whether human mesenchymal stem cells (MSC) are partly of donor origin in patients with SAA years after successful bone marrow transplant (BMT). Three SAA patients 3, 5, and 8 years after BMT (cyclophosphamide, ATG) with bone marrow from an HLA-identical sibling donor of the opposite sex were investigated. MSC were grown from patients' bone marrow aspirates according to Caplan et al. The number of MSC that were isolated from SAA bone marrow post transplant was about 10 times lower than in normal controls. Primary cultures of adherent MSC and passage-one cells were analyzed by dual-color interphase fluorescence in situ hybridization (FISH) analysis using centromere-specific DNA probes for X and Y chromosome. FISH did not show any clear evidence of donor cells in the adherent MSC: In all cases, less than 0.5% of nuclei showed a donor-type signal pattern that is well within assay limits. In a female patient, the absence of male donor cells was confirmed by sensitive and quantitative, Y chromosome-specific TaqMan PCR (QYCS-PCR). In contrast, Ficoll-separated hematopoietic cells from the same aspirates were greater than 90% of donor origin, as expected. In SAA, as previously found in patients with lysosomal and peroxisomal storage disease, bone marrow MSC remain host-derived despite successful hematopoietic engraftment years after allogeneic BMT.
AB - Stromal defects are part of the etiology of severe aplastic anemia (SAA), and hematopoietic engraftment is poor in unrelated and mismatched transplant. Therefore, we wanted to find out whether human mesenchymal stem cells (MSC) are partly of donor origin in patients with SAA years after successful bone marrow transplant (BMT). Three SAA patients 3, 5, and 8 years after BMT (cyclophosphamide, ATG) with bone marrow from an HLA-identical sibling donor of the opposite sex were investigated. MSC were grown from patients' bone marrow aspirates according to Caplan et al. The number of MSC that were isolated from SAA bone marrow post transplant was about 10 times lower than in normal controls. Primary cultures of adherent MSC and passage-one cells were analyzed by dual-color interphase fluorescence in situ hybridization (FISH) analysis using centromere-specific DNA probes for X and Y chromosome. FISH did not show any clear evidence of donor cells in the adherent MSC: In all cases, less than 0.5% of nuclei showed a donor-type signal pattern that is well within assay limits. In a female patient, the absence of male donor cells was confirmed by sensitive and quantitative, Y chromosome-specific TaqMan PCR (QYCS-PCR). In contrast, Ficoll-separated hematopoietic cells from the same aspirates were greater than 90% of donor origin, as expected. In SAA, as previously found in patients with lysosomal and peroxisomal storage disease, bone marrow MSC remain host-derived despite successful hematopoietic engraftment years after allogeneic BMT.
KW - Adult
KW - Anemia, Aplastic/pathology
KW - Bone Marrow Cells/cytology
KW - Bone Marrow Transplantation
KW - Cell Lineage
KW - Female
KW - Follow-Up Studies
KW - Graft Survival
KW - Hematopoiesis
KW - Humans
KW - Immunohistochemistry
KW - In Situ Hybridization, Fluorescence
KW - Male
KW - Mesoderm/cytology
KW - Middle Aged
KW - Stem Cells/cytology
KW - Transplantation Chimera
KW - Transplantation, Homologous
U2 - 10.1089/152581602321080646
DO - 10.1089/152581602321080646
M3 - Short publication
C2 - 12590713
VL - 11
SP - 977
EP - 984
JO - J HEMATOTH STEM CELL
JF - J HEMATOTH STEM CELL
SN - 1525-8165
IS - 6
ER -