Blood Res.  2018 Mar;53(1):61-70. 10.5045/br.2018.53.1.61.

Expression of adhesion molecules on CD34+ cells from steady-state bone marrow before and after mobilization and their association with the yield of CD34+ cells

• Cecyn KZ
• Kimura EY
• Lima DM
• Yamamoto M
• Bordin JO
• de Oliveira JSR

• KMID: 2414366
• DOI: http://doi.org/10.5045/br.2018.53.1.61

Abstract

BACKGROUND
Cell adhesion molecules (CAMs) expressed on hematopoietic progenitor cells (HPCs), endothelial cells, and stromal cells play a pivotal role in the mobilization of CD34+ cells. Herein, we conducted a non-randomized peripheral blood stem cell (PBSC) mobilization study aimed to compare the potential differences in the expressions of several CAMs and chemokines on CD34+ cells obtained from bone marrow aspirate before and after HPC mobilization from patients with hematologic malignancies and healthy donors.
METHODS
Three-color cytofluorometric analysis was used to compare the expressions of CAMs and chemokines in the bone marrow before and after mobilization.
RESULTS
For all studied groups, CAM expression among those with good and poor yields of CD34+ cells was significantly correlated with VCAM-1 (P=0.007), CD44 (P=0.027), and VLA-4 (P=0.014) expressions. VCAM-1 (P=0.001), FLT-3 (P=0.001), CD44 (P=0.011), VLA-4 (P=0.001), and LFA-1 (P=0.001) expressions were higher before HPC mobilization than after HPC mobilization. By contrast, the expression of CXCR4 significantly varied before and after mobilization only among those with successful PBSC mobilization (P=0.002).
CONCLUSION
We attempted to identify particular aspects of CAMs involved in CD34+ cell mobilization, which is a highly complex mechanism that involves adhesion molecules and matrix metalloproteases. The mechanism by which CD34+ cell mobilization is activated through proteolytic enzymes is not fully understood. We believe that CXCR4, VLA-4, CD44, and VCAM-1 are the most important molecules implicated in HPC mobilization, particularly because they show a correlation with the yield of CD34+ cells collected via large volume leukapheresis.

Keyword

Adhesion molecules; Hematopoietic progenitor cells; Mobilization; Stem cell donor; Multiple myeloma; Non-Hodgkin lymphoma

MeSH Terms

Bone Marrow*
Cell Adhesion Molecules
Chemokines
Endothelial Cells
Hematologic Neoplasms
Hematopoietic Stem Cells
Humans
Integrin alpha4beta1
Leukapheresis
Lymphocyte Function-Associated Antigen-1
Lymphoma, Non-Hodgkin
Metalloproteases
Multiple Myeloma
Peptide Hydrolases
Stem Cells
Stromal Cells
Tissue Donors
Vascular Cell Adhesion Molecule-1
Cell Adhesion Molecules
Chemokines
Integrin alpha4beta1
Lymphocyte Function-Associated Antigen-1
Metalloproteases
Peptide Hydrolases
Vascular Cell Adhesion Molecule-1

Figure

• 

  Fig. 1 Representative flow cytometric scattergrams from bone marrow aspirate specimens after HPC mobilization showing a 3-color cytofluorometric analysis of the expression of adhesion molecule antigens on CD34+ cells population. (A) CD34+ cells are painted in the lympho-mononuclear region. (B) CD34PE+ cells are included in R1 in the FSC/SSC dot plot. (C) CD34PE+ cells population in R2. (D) CD34FITC+ cells are included in R1 in the FSC/SSC dot plot. (E) CD34FITC+ cells population in R3. (F) CD34PE+ cells are included in R6 in the CD45PerCP/SSC dot plot. (G) CD34FITC+ cells are included in R6 in the CD45PerCP/SSC dot plot.

• 

  Fig. 2 Representative flow cytometric histograms from bone marrow aspirate specimens after HPC mobilization showing a 3-color cytofluorometric analysis of the expression of adhesion molecule antigen on CD34+ cell population. The results were estimated as the mean fluorescence intensity (MFI). The histograms (A) and (B) are IgG1 FITC and PE controls. (C) CD106, (D) CD135, (E) CD184, (F) CD62L, (G) CD49d, (H) CD11a, and (I) CD44 antigen on CD34+ cell population. The gating protocols have been described before.

• 

  Fig. 3 The mean expression of CD106, CD-44, and CD49d on the CD34+ cells assessed in BMA before mobilization and its association with the yield of CD34+ cells collected via LVL in both donors and patients.

• 

  Fig. 4 Distribution of CD106, CD135, CD11a, CD44, CD49d, and CD184 assessed in mononuclear cells of the BMA, before and after mobilization according to the yield of CD34+ cells obtained via LGV.

• 

  Fig. 5 Results obtained through logistic regression analysis. The chance of poor mobilization increases by approximately 6% with each increase of one unit of CD49d and by approximately 4% with each increase of one unit of CD44 in the pre-mobilization phase.

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