4th Palermo Conference on INNOVATIVE THERAPIES FOR LYMPHOID MALIGNANCIES
Published online 22 September 2009
Haematologica, Vol 94, Issue 12, 1649-1660 doi:10.3324/haematol.2009.006171
Copyright © 2009 by Ferrata Storti Foundation
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Hematopoietic Stem Cells

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

Maria Antonietta Avanzini1, Maria Ester Bernardo1, Angela Maria Cometa1, Cesare Perotti2, Nadia Zaffaroni3, Francesca Novara4, Livia Visai5, Antonia Moretta1, Claudia Del Fante2, Raffaella Villa3, Lynne M. Ball6, Willem E. Fibbe7, Rita Maccario1,8, Franco Locatelli1

1 Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Pavia, Italy
2 Servizio di Immunoematologia e Medicina Trasfusionale, Banca del Cordone Ombelicale, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
3 Dipartimento di Oncologia Sperimentale, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
4 Dipartimento di Patologia Umana ed Ereditaria, Sezione Biologia Generale e Genetica Medica, Università di Pavia, Pavia, Italy
5 Dipartimento di Biochimica and Center for Tissue Engineering (CIT), Università di Pavia, Pavia, Italy
6 Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands
7 Department of Immunohematology and Blood Transfusion, Center for Stem Cell Therapy, Leiden University Medical Center, Leiden, the Netherlands
8 Cell Factory, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

Correspondence: Maria Ester Bernardo, MD, Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, P. le Golgi 2, 27100 Pavia, Italy. E-mail: mebernardo{at}gmail.com

Background: Mesenchymal stromal cells are employed in various different 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 the cell source and culture conditions.

Design and Methods: We tested the ability of a 5% platelet lysate-supplemented medium to support isolation and ex vivo expansion of mesenchymal stromal cells from full-term umbilical-cord blood. We also investigated the biological/functional properties of umbilical cord blood mesenchymal stromal cells, in comparison with platelet lysate-expanded bone marrow mesenchymal stromal cells.

Results: The success rate of isolation of mesenchymal stromal cells from umbilical cord blood was in the order of 20%. These cells exhibited typical morphology, immunophenotype and differentiation capacity. Although they have a low clonogenic efficiency, umbilical cord blood mesenchymal stromal cells may possess high proliferative potential. The genetic stability of these cells from umbilical cord blood was demonstrated by a normal molecular karyotype; in addition, these cells do not express hTERT and telomerase activity, do express p16ink4a protein and do not show anchorage-independent cell growth. Concerning alloantigen-specific immune responses, umbilical cord blood mesenchymal stromal cells were able to: (i) suppress T- and NK-lymphocyte proliferation, (ii) decrease cytotoxic activity and (iii) only slightly increase interleukin-10, while decreasing interferon-{gamma} secretion, in mixed lymphocyte culture supernatants. While an indoleamine 2,3-dioxygenase-specific inhibitor did not reverse mesenchymal stromal cell-induced suppressive effects, a prostaglandin E2-specific inhibitor hampered the suppressive effect of both umbilical cord blood- and bone marrow-mesenchymal stromal cells on alloantigen-induced cytotoxic activity. Mesenchymal stromal cells from both sources expressed HLA-G.

Conclusions: Umbilical cord blood- and bone marrow-mesenchymal stromal cells may differ in terms of clonogenic efficiency, proliferative capacity and immunomodulatory properties; these differences may be relevant for clinical applications.

Key words: mesenchymal stromal cells, umbilical cord blood, platelet lysate, immunomodulatory properties, cell therapy.