This Article Full Text (PDF) Kuci et al. Supplementary Appendix Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kuçi, S. Articles by Bader, P. PubMed PubMed Citation Articles by Kuçi, S. Articles by Bader, P.

CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties

¹ University Children’s Hospital III, Department of Hematology/Oncology, Frankfurt am Main, Germany
² DRK Institute of Transfusion Medicine and Immune Hematology Frankfurt am Main, Germany
³ Miltenyi Biotec GmbH, Bergisch-Gladbach, Germany
⁴ Hartmann’s group, Institute of Molecular Pathology, Vienna, Austria
⁵ Biopharmaceutical Institute Georg-Speyer-Haus, Frankfurt am Main, Germany

Correspondence: Selim Kuçi, University Children’s Hospital III, Department of Hematology/Oncology, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. E-mail: selim.kuci{at}kgu.de

ABSTRACT

Background: In vitro proliferative and differentiation potential of mesenchymal stromal cells generated from CD271⁺ bone marrow mononuclear cells (CD271-MSCs) has been demonstrated in several earlier and recent reports. In the present study we focused, in addition to proliferative and differentiation potential, in vitro and in vivo immunosuppressive and lymphohematopoietic engraftment-promoting potential of these MSCs compared to bone marrow-derived MSCs generated by plastic adherence (PA-MSCs).

Design and Methods: We set up a series of experimental protocols in order to determine the phenotype of CD271-MSCs, their clonogenic, proliferative, differentiation and immunosuppressive potential. Potential of CD271-MSCs to improve the engraftment of CD133⁺ hematopoietic stem cells (HSCs) at cotransplantation was evaluated in immunodeficient NOD/SCID-IL2R^null mice.

Results: In vitro studies demonstrated that CD271-MSCs differentiate along adipogenic, osteogenic and chondrogenic lineage (trilineage potential), produce significantly higher levels of cytokines than PA-MSCs, and significantly inhibit the proliferation of allogeneic T-lymphocytes in mixed lymphocyte reaction assay. Elevated levels of prostaglandin E2, but not nitric monoxide, mediated the majority of this immunosuppressive effect. In vivo studies showed that CD271-MSCs promote a significantly greater lymphoid engraftment than PA-MSCs when cotransplanted with CD133⁺ HSCs at a ratio of 8:1 in immunodeficient NOD/SCID-IL2R^null mice. They induced a 10.4-fold increase in the number of T-cells, a 2.5-fold increase in the number of NK-cells, and a 3.6-fold increase in the number of B-cells, indicating major qualitative difference between these two MSC populations.

Conclusions: Our results indicate that CD271 antigen provides a versatile marker for prospective isolation and expansion of multipotent MSCs with immunosuppressive and lymphohematopoietic engraftment-promoting properties. Their cotransplantation with HSCs in patients with hematological malignancies may prove valuable in the prevention of impaired/delayed T-cell recovery and graft-versus-host disease.

Key words: T-cell recovery, graft-versus-host disease, MSCs.