Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors.
Mesenchymal stromal cells (MSC) provide a supportive cellular microenvironment and are able to maintain the self-renewal capacity of hematopoietic progenitor cells (HPC). Isolation procedures for MSC vary extensively, and this may influence their biologic properties. In this study, we have compared human MSC isolated from bone marrow (BM) using two culture conditions, from cord blood (CB), and from adipose tissue (AT). The ability to maintain long-term culture-initiating cell frequency and a primitive CD34(+)CD38(-) immunophenotype was significantly higher for MSC derived from BM and CB compared with those from AT. These results were in line with a significantly higher adhesion of HPC to MSC from BM and CB versus MSC from AT. We have compared the cytokine production of MSC by cytokine antibody arrays, enzyme-linked immunosorbent assay, and a cytometric bead array. There were reproducible differences in the chemokine secretion profiles of various MSC preparations, but there was no clear concordance with differences in their potential to maintain primitive function of HPC. Global gene expression profiles of MSC preparations were analyzed and showed that adhesion proteins including cadherin-11, N-cadherin, vascular cell adhesion molecule 1, neural cell adhesion molecule 1, and integrins were highly expressed in MSC preparations derived from BM and CB. Thus, MSC from BM and CB are superior to MSC from AT for maintenance of primitive HPC. The latter property is associated with specific molecular profiles indicating the significance of cell-cell junctions but not with secretory profiles. Disclosure of potential conflicts of interest is found at the end of this article.
Wagner
Wolfgang
W
Department of Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. wolfgang_wagner@med.uni-heidelberg.de
Roderburg
Christoph
C
Wein
Frederik
F
Diehlmann
Anke
A
Frankhauser
Maria
M
Schubert
Ralf
R
Eckstein
Volker
V
Ho
Anthony D
AD
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000273:Adipose Tissue / Q000166:cytology; D018952:Antigens, CD34 / Q000032:analysis; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002450:Cell Communication; D018929:Cell Culture Techniques / Q000379:methods; D002469:Cell Separation; D002478:Cells, Cultured / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000494:pharmacology; D007365:Intercellular Junctions / Q000502:physiology; D008648:Mesoderm / Q000166:cytology*; D009928:Organ Specificity; D017154:Stromal Cells / Q000378:metabolism*
D018952:Antigens, CD34; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018969:Insulin-Like Growth Factor Binding Proteins; D051997:ADP-ribosyl Cyclase 1