Association of an Impaired Bone Marrow Microenvironment with Secondary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation Yuan.

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Association of an Impaired Bone Marrow Microenvironment with Secondary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation Yuan Kong, Ying-Jun Chang, Ya-Zhe Wang, Yu-Hong Chen, Wei Han, Yu Wang, Yu-Qian Sun, Chen-Hua Yan, Feng-Rong Wang, Yan- Rong Liu, Lan-Ping Xu, Dai-Hong Liu, Xiao-Jun Huang Biology of Blood and Marrow Transplantation Volume 19, Issue 10, Pages 1465-1473 (October 2013) DOI: 10.1016/j.bbmt.2013.07.014 Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 BMB cellularity was significantly lower in the patients with secondary PGF (A3) compared with the patients with GGF (A2) and the HDs (A1). Original magnification, 10×. Biology of Blood and Marrow Transplantation 2013 19, 1465-1473DOI: (10.1016/j.bbmt.2013.07.014) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Percentages of CD34+ cells (B), perivascular cells (C), and EPCs (D) in the BM were significantly lower in patients with secondary PGF compared with those with GGF and HDs, even though there was no difference in transplanted CD34+ cell dose between the secondary PGF and GGF groups (A). Statistical analyses were done using 1-way ANOVA. MNCs, mononuclear cells. Biology of Blood and Marrow Transplantation 2013 19, 1465-1473DOI: (10.1016/j.bbmt.2013.07.014) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Immunophenotypic analysis of perivascular cells within the human BM microenvironment. Shown are representative FACS analyses of CD45-CD34-CD146+ perivascular cells from an HD donor (A), a patients with GGF (B), and a patient with secondary PGF (C). Biology of Blood and Marrow Transplantation 2013 19, 1465-1473DOI: (10.1016/j.bbmt.2013.07.014) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Immunophenotypic analysis of EPCs within the human BM microenvironment. Representative FACS gating strategies of CD45-CD34+VEGFR2+ EPCs are shown in an HD. Biology of Blood and Marrow Transplantation 2013 19, 1465-1473DOI: (10.1016/j.bbmt.2013.07.014) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 In situ expression of hematopoietic niche marker by endosteal cells in human BMBs. The trabecular bone was lined by fewer detectable endosteal cells in patients with secondary PGF compared with patients with GGF and HDs, as evaluated by H&E (A1-A3) and IHC staining with osteopontin (B1-B3). Original magnification, 40×. Red arrows indicate endosteal cells. Biology of Blood and Marrow Transplantation 2013 19, 1465-1473DOI: (10.1016/j.bbmt.2013.07.014) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 6 In situ expression of hematopoietic niche marker by sinusoidal endothelial cells in human BMBs. Significantly fewer microvessels were detected in the patients with secondary PGF compared with those with GGF and HDs, as evaluated by H&E (A1-A3) and IHC staining with CD34 (B1-B3). Original magnification, 40×. Red arrows indicate microvessels. Biology of Blood and Marrow Transplantation 2013 19, 1465-1473DOI: (10.1016/j.bbmt.2013.07.014) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 7 In situ expression of hematopoietic niche marker by perivascular cells in human BMBs. The patients with secondary PGF had fewer perivascular cells surrounding microvessels compared with patients with GGF and HDs, as demonstrated by IHC with CD146 (A1-A3). Original magnification, 40×. Red arrows indicate perivascular cells. Biology of Blood and Marrow Transplantation 2013 19, 1465-1473DOI: (10.1016/j.bbmt.2013.07.014) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions