title: Clonal analysis of multipotent stromal cells derived from CD271+ bone marrow mononuclear cells: functional heterogeneity and different mechanisms of allosuppression.
abstract: Previous reports demonstrated a relationship between proliferation potential and trilineage differentiation in mesenchymal stromal cell-derived clones generated using plastic adherence (PA-MSCs). However, there are no reports presenting a clonal analysis of the proliferative potential, differentiation potential and allosuppressive effects of human mesenchymal stromal cell subsets. In this study, we performed a clonal analysis of mesenchymal stromal cells generated from human CD271(+) bone marrow mononuclear cells (CD271-MSCs). After transfection with the gene encoding green fluorescent protein, the cells were single-cell sorted and cultured for 2-4 weeks. A population doubling analysis demonstrated that 25% of CD271-MSC clones are fast-proliferating clones compared to only 10% of PA-MSC clones. Evaluation of the allosuppressive potential demonstrated that 81.8% of CD271-MSC clones were highly allosuppressive compared to only 58% of PA-MSC clones. However, no consistent correlation was observed between allosuppression and proliferative potential. Prostaglandin E2 levels were positively correlated with the allosuppressive activity of individual clones, suggesting that this molecule may be a useful predictive biomarker for the allosuppressive potential of mesenchymal stromal cells. In contrast, inhibitory studies of indoleamine 2,3 dioxygenase indicated that none of the clones used this enzyme to mediate their allosuppressive effect. Differentiation studies revealed the presence of tripotent, bipotent and unipotent CD271-MSC and PA-MSC clones which suppressed the allogeneic reaction to differing extents in vitro. In conclusion, our findings demonstrate differences between CD271-MSCs and PA-MSCs and indicate that neither proliferation potential nor differentiation potential represents a consistent predictive parameter for the immunomodulatory effects of either type of mesenchymal stromal cells.
authors: selim.kuci@kgu.de.
authors: Zyrafete
authors: Z
authors: Kuçi
authors: Julia
authors: J
authors: Seiberth
authors: Hatixhe
authors: H
authors: Latifi-Pupovci
authors: Sibylle
authors: S
authors: Wehner
authors: Stefan
authors: S
authors: Stein
authors: Manuel
authors: M
authors: Grez
authors: Halvard
authors: H
authors: Bönig
authors: Ulrike
authors: U
authors: Köhl
authors: Thomas
authors: T
authors: Klingebiel
authors: Peter
authors: P
authors: Bader
authors: Selim
authors: S
authors: Kuçi
mesh_terms: D001854:Bone Marrow Cells / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D039902:Multipotent Stem Cells / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology
chemical_list: C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor
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