TY - JOUR
T1 - A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β
AU - Hatzfeld, A.
AU - Eid, P.
AU - Peiffer, I.
AU - Li, M. L.
AU - Barbet, R.
AU - Oostendorp, R. A.J.
AU - Haydont, V.
AU - Monier, M. N.
AU - Milon, L.
AU - Fortunel, N.
AU - Charbord, P.
AU - Tovey, M.
AU - Hatzfeld, J.
N1 - Funding Information:
This work was supported by the European Integrated Project (PCRD6) ‘GENOSTEM’: ‘Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to the bed side’. Contract no: 503161. RB, MLL and IP were appointed by the Genostem Project. We are indebted to Dr Mary Osborne-Pellegrin for editing the paper.
PY - 2007/4
Y1 - 2007/4
N2 - Type I interferon (IFN) is shown to control the reversible quiescence of a primitive human bone marrow mesenchymal stem cell (MSC) subpopulation. A 24h 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-IFNα 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.
AB - Type I interferon (IFN) is shown to control the reversible quiescence of a primitive human bone marrow mesenchymal stem cell (MSC) subpopulation. A 24h 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-IFNα 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.
UR - http://www.scopus.com/inward/record.url?scp=33947393200&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2404589
DO - 10.1038/sj.leu.2404589
M3 - Article
C2 - 17375123
AN - SCOPUS:33947393200
SN - 0887-6924
VL - 21
SP - 714
EP - 724
JO - Leukemia
JF - Leukemia
IS - 4
ER -