Background Mesenchymal stromal cells (MSCs) are employed in diverse clinical settings in order to modulate immune response. However, relatively little is known about the mechanisms responsible for their immunomodulatory effects, which could be influenced by both cell source and culture conditions. DESIGN AND METHODS: We tested the ability of a 5% platelet lysate (PL)-supplemented medium to support isolation and ex vivo expansion of MSCs from full-term umbilical-cord blood (UCB). We also investigated the biological/functional properties of UCB-MSCs, in comparison with PL-expanded bone marrow (BM)-MSCs. RESULTS: Success rate of MSC isolation from UCB was in the order of 20%. UCB-MSCs exhibited the typical morphology, immunophenotype and differentiation capacity. Although they have a low clonogenic efficiency, UCB-MSCs may possess high proliferative potential. The genetic stability of UCB-MSCs was demonstrated by a normal molecular karyotype; in addition, these cells do not express hTERT and telomerase activity, express p16ink4a protein and do not show anchorage-independent cell growth. Concerning alloantigen-specific immune response, UCB-MSCs were able to: i) suppress T- and NK-lymphocyte proliferation, ii) decrease cytotoxic activity and iii) only slightly increase IL-10, while decreasing IFNgamma secretion, in mixed lymphocyte culture (MLC) supernatants. While an IDO-specific inhibitor did not reverse MSC-induced suppressive effects, a PGE2-specific inhibitor hindered the suppressive effect of both UCB- and BM-MSCs on alloantigen-induced cytotoxic activity. Both UCB- and BM-MSCs expressed HLA-G. Conclusions UCB- and BM-MSCs may differ in terms of clonogenic efficiency, proliferative capacity and immunomodulatory properties; these differences may be relevant for clinical application.

Generation of mesenchymal stromal cells in the presence of platelet lysate: a phenotypical and functional comparison of umbilical cord blood- and bone marrow-derived progenitors.

VISAI, LIVIA;LOCATELLI, FRANCO
2009-01-01

Abstract

Background Mesenchymal stromal cells (MSCs) are employed in diverse clinical settings in order to modulate immune response. However, relatively little is known about the mechanisms responsible for their immunomodulatory effects, which could be influenced by both cell source and culture conditions. DESIGN AND METHODS: We tested the ability of a 5% platelet lysate (PL)-supplemented medium to support isolation and ex vivo expansion of MSCs from full-term umbilical-cord blood (UCB). We also investigated the biological/functional properties of UCB-MSCs, in comparison with PL-expanded bone marrow (BM)-MSCs. RESULTS: Success rate of MSC isolation from UCB was in the order of 20%. UCB-MSCs exhibited the typical morphology, immunophenotype and differentiation capacity. Although they have a low clonogenic efficiency, UCB-MSCs may possess high proliferative potential. The genetic stability of UCB-MSCs was demonstrated by a normal molecular karyotype; in addition, these cells do not express hTERT and telomerase activity, express p16ink4a protein and do not show anchorage-independent cell growth. Concerning alloantigen-specific immune response, UCB-MSCs were able to: i) suppress T- and NK-lymphocyte proliferation, ii) decrease cytotoxic activity and iii) only slightly increase IL-10, while decreasing IFNgamma secretion, in mixed lymphocyte culture (MLC) supernatants. While an IDO-specific inhibitor did not reverse MSC-induced suppressive effects, a PGE2-specific inhibitor hindered the suppressive effect of both UCB- and BM-MSCs on alloantigen-induced cytotoxic activity. Both UCB- and BM-MSCs expressed HLA-G. Conclusions UCB- and BM-MSCs may differ in terms of clonogenic efficiency, proliferative capacity and immunomodulatory properties; these differences may be relevant for clinical application.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/201697
Citazioni
  • ???jsp.display-item.citation.pmc??? 41
  • Scopus 115
  • ???jsp.display-item.citation.isi??? 101
social impact