Characterization of Hemopoietic Stem Cell Chimerism in Antibody-Facilitated Bone Marrow Chimeras

Lh, Francescutti; Gambel, Phillip; Tg, Wegmann

doi:10.1097/00007890-198507000-00002

Cited by 7 publications

(3 citation statements)

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“…The results of this in situ immunofluorescence analysis demonstrated that 90% of the adherent cells in LTBC, from both radiation and completely reconstituted WX/IW' chimeras, were donor derived, and thus are predominantly transplantable cells of hematopoietic origin. Independent GPI electrophoretic analyses ofwhole adherent layers from these chimeras also showed that 70-95% of the adherent cells are donor in origin, which agrees with previous studies that used strain-specific enzyme markers in antibody-facilitated and radiation chimeras (7,23,24).…”

Section: Discussionsupporting

confidence: 89%

Hematopoietic microenvironment. Origin, lineage, and transplantability of the stromal cells in long-term bone marrow cultures from chimeric mice.

Perkins

Fleischman²

1988

J. Clin. Invest.

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Studies of bone marrow transplant patients have suggested that the stromal cells of the in vitro hematopoietic microenvironment are transplantable into conditioned recipients. Moreover, in patients with myeloproliferative disorders, all of the stromal cells, which include presumptive endothelial cells, appear to be derived from hematopoietic precursors. To confirm these findings, we have constructed two chimeric mouse models: (a) traditional radiation chimeras, and (b) fetal chimeras, produced by placental injection of bone marrow into genetically anemic WX/WV fetuses, a technique that essentially precludes engraftment of nonhematopoietic cells. Using two-color indirect immunofluorescence, the stromal cells in long-term bone marrow culture derived from these chimeras were analyzed for donor or host origin by strain-specific H-2 antigens, and for cell lineage by a variety of other specific markers. 75-95% of the stromal cells were shown to be hematopoietic cells of the monocyte-macrophage lineage, based upon donor origin, phagocytosis, and expression of specific hematopoietic surface antigens. The remaining 5-25% of the stromal cells were exclusively host in origin. Apart from occasional fat cells, these cells uniformly expressed collagen type IV, laminin, and a surface antigen associated with endothelial cells. Since these endothelial-like cells are not transplantable into radiation or fetal chimeras, they are not derived from hematopoietic stem cells. The contrast between our findings and human studies suggests either unexpected species differences in the origin of stromal lineages or limitations in the previous methodology used to detect nonhematopoietic stromal cells.

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Section: Discussionsupporting

confidence: 89%

Hematopoietic microenvironment. Origin, lineage, and transplantability of the stromal cells in long-term bone marrow cultures from chimeric mice.

Perkins

Fleischman²

1988

J. Clin. Invest.

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“…Hemoglobin and carbonic anhydrase are erythrocyte-specific enzymes and can therefore not be used for measuring engraftment along other lineages. Other biochemical markers that can be used to measure engraftment in all cells are the glycolytic enzymes phosphoglycerate kinase [21][22][23] or glucose-phosphate isomerase (Gpi) [24][25][26][27]; these can be used in congenically marked syngeneic as well as allogeneic (MHC-matched and mismatched) BMT. Two murine forms of the above enzymes exist that can be separated using electrophoresis and the relative contribution of donor and host stem cells to hematopoiesis can be determined in all cell lineages.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of Ly5 (CD45)‐Antigens Hampers Long‐Term Engraftment Following Minimal Conditioning in a Murine Bone Marrow Transplantation Model

Sheridan

Robinson

et al. 2001

STEM CELLS

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Various techniques are available for distinguishing donor from host cells evaluating the efficacy of conditioning regimen for experimental bone marrow transplantation (BMT). Techniques include the use of extracellular immunological markers, such as Ly5 (CD45), and intracellular biochemical markers, such as glucose-phosphate-isomerase (Gpi). Because Ly5 is an extracellular protein, the disparity between donor (Ly5.1) and host (Ly5.2) antigens may induce a weak immune response whereas with Gpi, no immune response is expected. This difference may be of particular concern in experimental transplantation approaches that use minimal conditioning such as low-dose total body irradiation (TBI). Such mild conditioning may not induce the immunosuppression required to overcome host rejection of Ly5 disparate cells.To ). However, when higher TBI or BMC doses were used, similar engraftment levels were found, suggesting sufficient immune suppression to allow equal engraftment of both sources of BM.These data suggest that even a minor phenotypic disparity between donor and host, such as Ly5, may necessitate high-dose TBI to prevent rejection. The combination of low-dose TBI or other nonmyeloablative conditioning strategies with small numbers of BMC may lead to reduced engraftment when extracellular immunological markers such as Ly5 are used for transplantation studies. Therefore, small immunological differences must be considered when using the Ly5 marker for engraftment.

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“…1984, Hollings et a/. 1984, Chertkov et al 1985, Francescutti, Gambel& Wegmann 1985, Hill et al 1986, Walker et al 1986). The stromal alterations noted in the syngeneic transplants would favour this damage being caused by the conditioning and the posttransplantation treatment.…”

Section: Discussionmentioning

confidence: 99%

Histopathology of bone marrow reconstitution after allogeneic bone marrow transplantation

Berg

Kluin

Zwaan³

et al. 1989

Histopathology

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In order to study haematopoietic reconstitution in allogeneic bone marrow transplantation we investigated bone marrow histology in 61 biopsies of 37 patients, treated with HLA-compatible bone marrow grafts for leukaemia or severe aplastic anaemia. The biopsies were taken from the day of transplantation until 100 d after transplantation. Stromal changes, in particular oedema, fibrosis and granulomas, were found during the whole period of observation. These changes were more prominent in biopsies from leukaemia patients than from patients with aplastic anaemia. The cellularity in the biopsies increased until 28 d after bone marrow transplantation and was stable thereafter. Initially, only clusters of cells belonging to a single cell lineage were seen, suggesting that the first outgrowth of haematopoietic cells is by proliferation of committed precursor cells. Long-lasting abnormalities in localization of haematopoietic cells in the bone marrow space and of the myeloid: erythroid ratio were seen; dyserythropoiesis was common.

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Characterization of Hemopoietic Stem Cell Chimerism in Antibody-Facilitated Bone Marrow Chimeras

Cited by 7 publications

References 0 publications

Hematopoietic microenvironment. Origin, lineage, and transplantability of the stromal cells in long-term bone marrow cultures from chimeric mice.

Hematopoietic microenvironment. Origin, lineage, and transplantability of the stromal cells in long-term bone marrow cultures from chimeric mice.

Immunogenicity of Ly5 (CD45)‐Antigens Hampers Long‐Term Engraftment Following Minimal Conditioning in a Murine Bone Marrow Transplantation Model

Histopathology of bone marrow reconstitution after allogeneic bone marrow transplantation

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