Adipose tissue-derived stromal cells retain immunosuppressive and angiogenic activity after coculture with cord blood hematopoietic precursors

Abstract

Adipose-tissue derived stromal cells (ASCs) are currently considered as a full value alternative source of bone marrow MSCs for prevention of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation due to their immunosuppressive potential. Besides, ASCs are known to support ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs). Ex vivo expansion enables to amplify significantly the number of HSPCs of different commitment. Mononuclear cells (MNCs) from cord blood (cb) contain HSPCs and are easily assessed. The rarity of those HSPCs is a serious limitation of its application in cell therapy. Here we expanded cbMNCs in stroma-dependent setting to generate heterocellular associates consisting of ASCs and undifferentiated and low committed hematopoietic cbHSPCs. A part of cbHSPCs in associates demonstrated a primitive phenotype confirmed by formation of “cobblestone areas". ASCs associated with cbHSPCs demonstrated up-regulation of immunosuppressive indoleamine 2,3-dioxygenase (IDO), leukemia inhibitory factor (LIF), cyclooxygenase-2 (PTGS2) genes. ASC-cbHSPCs as well as ASCs provoked the suppression of HLA-DR activation and apoptosis of mitogen-stimulated T cells. VEGF transcription and secretion were elevated providing stimulation of blood vessel formation in ovo.Thus, ASCs retain immunosuppressive and proangiogenic capacities evidencing “third party” potential along with the effective support of ex vivo expansion of cbHSPCs. Above functions expand the relevance of ASCs for needs of regenerative medicine.