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REVIEW

The role of novel and known extracellular matrix and adhesion molecules in the homeostatic and regenerative bone marrow microenvironment

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Pages 563-577 | Received 08 Apr 2014, Accepted 30 Jun 2014, Published online: 26 Jan 2015

Figures & data

Table 1. Differential expression of adhesion molecules in HSPCs during BM regeneration10,175, HSPC differentiation11 and development10,174 The analyzed mRNA targets are in the first column. The second column depicts the change in mRNA in murine BM HSPCs after 5-fluorouracil (5FU) treatment, G-CSF treatment or combined G-CSF and cyclophosphamide (Cy) treatment.Citation5,10,17 The second column depicts how the mRNA expression in short-term HSPCs relates to that in long-term HSPCs in the murine BM.Citation11 The third column represents the difference in mRNA expression between HSPCs isolated from the fetal-liver or the fetal-BM.Citation4,10,17 The last column indicates the differential mRNA expression of adhesion molecules as determined on different sources of human CD34+ cells as depicted in . Arrows in green boxes mean increased mRNA expression, arrows in red boxes mean decreased mRNA expression. NS = not significant

Figure 1. Relative mRNA expression of adhesion molecules in HSPCs from BM, cord blood (CB) and mobilized peripheral blood (MPB). CD34+ cells were isolated using a MACS cell separation kit from Miltenyi Biotec. Cells were lysed and mRNA was isolated using a Qiagen mRNA isolation kit. c-DNA was prepared and the mRNA was quantified using a StepOnePlus Taqman machine. The mRNA expression was calculated relative to the GUS mRNA expression in each sample, by use of the 2−(ΔCt) value. Subsequently, the expression of each gene was depicted relative to its expression in BM HSPCs. Statistics were performed using a Student T-test. n ≥ 5 for MPB; n ≥ 4 for BM; n ≥ 5 for CB; bars represent mean ± SEM. * means P > 0.05.

Figure 1. Relative mRNA expression of adhesion molecules in HSPCs from BM, cord blood (CB) and mobilized peripheral blood (MPB). CD34+ cells were isolated using a MACS cell separation kit from Miltenyi Biotec. Cells were lysed and mRNA was isolated using a Qiagen mRNA isolation kit. c-DNA was prepared and the mRNA was quantified using a StepOnePlus Taqman machine. The mRNA expression was calculated relative to the GUS mRNA expression in each sample, by use of the 2−(ΔCt) value. Subsequently, the expression of each gene was depicted relative to its expression in BM HSPCs. Statistics were performed using a Student T-test. n ≥ 5 for MPB; n ≥ 4 for BM; n ≥ 5 for CB; bars represent mean ± SEM. * means P > 0.05.

Figure 2. Model of the endosteal, arteriolar and vascular bone marrow niches. The arteriolar niche localizes close to the endosteum and harbours mostly quiescent HSCs, whereas the sinusoidal niches are distributed throughout the BM and harbour mostly HSPCs that are in cell cycle. During haematopoietic regeneration after myeloablation, HSPCs proliferate and are mostly localized in sinusoidal niches. A range of ECM and matrix-associated molecules are differentially expressed upon BM regeneration. BIGH3 (purple dots) expression in HSPCs is upregulated in regenerative BM, suggesting its expression is dominant in sinusoidal HSPCs. BIGH3 expression is higher in BM-derived HSPCs compared to MPB-derived HSPCs, indicating that its expression is down-regulated upon transmigration into the blood. Adapted by permission from Macmillan Publishers, Ltd, http://www.nature.com/nri/posters, 2007 volume 7 no. 6 (T. Graf and A. Trumpp)

Figure 2. Model of the endosteal, arteriolar and vascular bone marrow niches. The arteriolar niche localizes close to the endosteum and harbours mostly quiescent HSCs, whereas the sinusoidal niches are distributed throughout the BM and harbour mostly HSPCs that are in cell cycle. During haematopoietic regeneration after myeloablation, HSPCs proliferate and are mostly localized in sinusoidal niches. A range of ECM and matrix-associated molecules are differentially expressed upon BM regeneration. BIGH3 (purple dots) expression in HSPCs is upregulated in regenerative BM, suggesting its expression is dominant in sinusoidal HSPCs. BIGH3 expression is higher in BM-derived HSPCs compared to MPB-derived HSPCs, indicating that its expression is down-regulated upon transmigration into the blood. Adapted by permission from Macmillan Publishers, Ltd, http://www.nature.com/nri/posters, 2007 volume 7 no. 6 (T. Graf and A. Trumpp)