Figure 4
BM stromal cells are the relevant source of SPARC in the development of experimental BM fibrosis. BM chimeras were obtained by transplanting WT and Sparc−/− mice with either WT or Sparc−/− BM cells to obtain WT > WT, Sparc−/− > WT, WT > Sparc−/−, and Sparc−/− > Sparc−/− BM chimeras. Chimeras were treated with either recombinant TPO to induce myeloproliferation and fibrosis or medium alone as a control (n = 5 mice per group, per experiment). The data shown represent 1 experiment of the 3 performed. (A) Histopathologic analysis of BM samples from TPO-treated BM chimeras. Hematoxylin and eosin staining shows signs of myeloproliferation in all of the different types of BM chimeras, which include marked granulocytic and megakaryocytic hyperplasia with MK clustering (hematoxylin and eosin panels). A considerable degree of dysgranulopoiesis and megakaryocytic atypia is observed in chimeras with a Sparc−/− recipient (WT > Sparc−/−, Sparc−/− > Sparc−/−). Gomori staining shows a significant degree of stromal fibrosis only in BM chimeras in which the recipient is WT (WT > WT, Sparc−/− > WT), as highlighted by the presence of an intricate network of black-stained fibers (Gomori panels, black arrows). By contrast, no stromal fibrosis is detected in TPO-treated chimeras in which the recipient is Sparc−/−, irrespective of Sparc genotype of the donor. Original magnifications ×400. Scale bars represent 50 μm. (B) Histopathologic analysis of the splenic architecture of control and TPO-treated chimeric mice showing that the splenic parenchyma of treated mice is characterized by effacement of the white pulp (WP) because of the expansion of the red pulp (RP) with prominent megakaryocytic hyperplasia and clustering (insets). Original magnifications ×100, insets ×200. Scale bars represent 200 μm. (C) Grading of BM fibrosis in TPO-treated BM chimeric mice was performed on Gomori-stained BM sections according to a 4-grade semiquantitative scoring system (see “Histopathology and immunohistochemistry”). The mean grade of fibrosis is significantly higher in TPO-treated chimeric mice with a WT recipient than in those with Sparc−/− recipients. **P < .01.

BM stromal cells are the relevant source of SPARC in the development of experimental BM fibrosis. BM chimeras were obtained by transplanting WT and Sparc−/− mice with either WT or Sparc−/− BM cells to obtain WT > WT, Sparc−/− > WT, WT > Sparc−/−, and Sparc−/− > Sparc−/− BM chimeras. Chimeras were treated with either recombinant TPO to induce myeloproliferation and fibrosis or medium alone as a control (n = 5 mice per group, per experiment). The data shown represent 1 experiment of the 3 performed. (A) Histopathologic analysis of BM samples from TPO-treated BM chimeras. Hematoxylin and eosin staining shows signs of myeloproliferation in all of the different types of BM chimeras, which include marked granulocytic and megakaryocytic hyperplasia with MK clustering (hematoxylin and eosin panels). A considerable degree of dysgranulopoiesis and megakaryocytic atypia is observed in chimeras with a Sparc−/− recipient (WT > Sparc−/−, Sparc−/− > Sparc−/−). Gomori staining shows a significant degree of stromal fibrosis only in BM chimeras in which the recipient is WT (WT > WT, Sparc−/− > WT), as highlighted by the presence of an intricate network of black-stained fibers (Gomori panels, black arrows). By contrast, no stromal fibrosis is detected in TPO-treated chimeras in which the recipient is Sparc−/−, irrespective of Sparc genotype of the donor. Original magnifications ×400. Scale bars represent 50 μm. (B) Histopathologic analysis of the splenic architecture of control and TPO-treated chimeric mice showing that the splenic parenchyma of treated mice is characterized by effacement of the white pulp (WP) because of the expansion of the red pulp (RP) with prominent megakaryocytic hyperplasia and clustering (insets). Original magnifications ×100, insets ×200. Scale bars represent 200 μm. (C) Grading of BM fibrosis in TPO-treated BM chimeric mice was performed on Gomori-stained BM sections according to a 4-grade semiquantitative scoring system (see “Histopathology and immunohistochemistry”). The mean grade of fibrosis is significantly higher in TPO-treated chimeric mice with a WT recipient than in those with Sparc−/− recipients. **P < .01.

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