Human mesenchymal stem cells improve ex vivo expansion of adult human CD34+ peripheral blood progenitor cells and decrease their allostimulatory capacity.
OBJECTIVE
Bone marrow mesenchymal stem cells (MSC) participate in the bone marrow microenvironment by providing growth factors and matrix proteins, which play a role in the regulation of hematopoiesis, through cell-to-cell interactions. Recently, MSC have been demonstrated to improve expansion of cord blood heamtopoietic stem cells (HSC).


METHODS
In this report, we evaluated the impact of MSC on ex vivo expansion of adult mobilized peripheral blood stem cells (PBSC). Moreover, the effect of MSC on the expanded PBSC allostimulatory capacity was also investigated, due to the well-known immunomodulatory properties of MSC. In addition, the requirement for cell-cell contact in this MSC coculture system was investigated using a transwell system.


RESULTS
Our results show that MSC greatly improved the expansion rate of adult PBSC cells relative to the absolute number of 1) clonogenic cells, 2) long-term cultured cells, or 3) CD34(+) cells. Whereas high levels of IL-6 on its own was sufficient to significantly improve PBSC expansion, direct contact between MSC and PBSC was required to achieve maximal expansion. Finally, MSC decreased the allostimulatory capacity of expanded PBSC.


CONCLUSIONS
Our data show that MSC efficiently improve expansion of adult PBSC, together with decreasing their allostimulatory capacity. Therefore, this study should provide a clinically relevant method for optimizing PBSC ex-vivo expansion, in particular when poor grafts are obtained.
Li
Na
N
Laboratoire d'Ingénierie et de Thérapie Cellulaire et Tissulaire, Faculté de Médecine, Université Henri Poincaré, Nancy, France.
Feugier
Pierre
P
Serrurrier
Brigitte
B
Latger-Cannard
Veronique
V
Lesesve
Jean-François
JF
Stoltz
Jean-François
JF
Eljaafari
Assia
A
D018952:Antigens, CD34 / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*
D018952:Antigens, CD34; D015850:Interleukin-6