A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β

Abstract

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 þ / 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-IFNa antibody, resulted in a marked increase in the number of very large colonies (CFU-F 43000 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.

A novel method for the isolation of subpopulations of rat adipose stem cells with different proliferation and osteogenic differentiation potentials

“…The presence of subpopulations is not a new finding regarding MSCs, as this has been widely reported for BM‐MSCs (Nasef et al , 2009; Hatzfeld et al , 2007; Liu et al , 2006). However, to our knowledge, the present study reports for the first time results demonstrating that adipose stem cells are composed of subpopulations.…”

The uncertain role of unmodified mesenchymal stem cells in tumor progression: what master switch?

“…MSCs are highly heterogeneous and differ in their surface marker composition, shape and capacity for proliferation and differentiation [44]. It is possible that only a subset of MSCs within a population possesses multipotent differentiation potential and promotes tumorigenesis, while another subset inhibits tumorigenesis.…”

Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived Mesenchymal Stem Cells and Human Mesenchymal Stem Cells

“…In a previous study [8], we observed that a 24 h pretreatment of Stro1+/GlycoA− or CD45−/GlycoA− hMSCs with a monoclonal antibody blocking the human type I interferon-alpha (IFN α ) receptor, or with a polyclonal anti-IFN α antibody, resulted in a marked increase in the number of very large colonies (Colony-forming Units-fibroblasts containing more than 3000 cells). Interestingly, these activated High Proliferative Potential-Quiescent hMSCs (HPP-Q hMSCs) expressed SSEA-3 and -4 at a higher level than non-pretreated cells, suggesting that HPP-Q hMSCs constituted a more primitive cell population than nontreated cells.…”