A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon alpha/beta.
Type I interferon (IFN) is shown to control the reversible quiescence of a primitive human bone marrow mesenchymal stem cell (MSC) subpopulation. A 24 h pre-treatment of Stro1+/GlycoA- or CD45-/GlycoA- subpopulations with a monoclonal antibody (mAb) against the IFNAR1 chain of the human type I IFN receptor (64G12), or with a polyclonal anti-IFNalpha antibody, resulted in a marked increase in the number of very large colonies (CFU-F >3000 cells) obtained in the presence of low, but necessary, concentrations of bFGF. Over a 2-month culture period, this short activation promoted a faster and greater amplification of mesenchymal progenitors for adipocytes and osteoblasts. Activation correlated with inhibition of STAT1 and STAT2 phosphorylation and of STAT1 nuclear translocation. A non-neutralizing anti-IFNAR1 mAb was ineffective. We demonstrate that control and activated MSCs express ST3GAL3, a sialyltransferase necessary to produce the embryonic antigens SSEA-3 and -4. Interestingly, activated MSC progeny expressed SSEA-3 and -4 at a higher level than control cultures, but this was not correlated with a significant expression of other embryonic markers. As MSCs represent an essential tool in tissue regeneration, the use of 64G12, which rapidly recruits a higher number of primitive cells, might increase amplification safety for cell therapy.
Peiffer
I
I
CNRS Human Stem Cell Laboratory, rue Guy Moquet, Villejuif, France. hatzfeld@vjf.cnrs.fr
Eid
P
P
Barbet
R
R
Li
M L
ML
Oostendorp
R A J
RA
Haydont
V
V
Monier
M-N
MN
Milon
L
L
Fortunel
N
N
Charbord
P
P
Tovey
M
M
Hatzfeld
J
J
Hatzfeld
A
A
D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D017931:DNA Primers; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000502:physiology*; D016899:Interferon-beta / Q000502:physiology*; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D016133:Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D017931:DNA Primers; D016898:Interferon-alpha; D053773:Transforming Growth Factor beta1; D016899:Interferon-beta