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Cord Blood Stem Cells

Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation

Bone Marrow Transplantation volume 46, pages 200–207 (2011)Cite this article

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Abstract

When compared with BMT, umbilical cord blood transplantation (UCBT) is associated with a lower rate of engraftment and delayed hematological/immunological recovery. This leads to increased risk of TRM in the early post transplantation period due to infection. Acute GVHD, although occurring less frequently in UCBT compared with BMT, is also significantly associated with increased rate of early TRM. BM MSCs are known to support normal in vivo hematopoiesis, and co-transplantation of MSCs has been shown to enhance engraftment of human cord blood hematopoietic cells in nonobese diabetic/SCID mice. In 13 children with hematological disorders (median age 2 years) undergoing UCBT, we co-transplanted paternal, HLA-disparate MSCs with the aim of improving hematological recovery and reducing rejection. We observed no differences in hematological recovery or rejection rates compared with 39 matched historical controls, most of whom received G-CSF after UCBT. However, the rate of grade III and IV acute GVHD was significantly decreased in the study cohort when compared with controls (P=0.05), thus resulting in reduced early TRM. Although these data do not support the use of MSCs in UCBT to support hematopoietic engraftment, they suggest that MSCs, possibly because of their immunosuppressive effect, may abrogate life-threatening acute GVHD and reduce early TRM.

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Acknowledgements

We acknowledge the cooperation of patients and families who have participated to date in this study, the medical and ancillary staff associated with the transplant centers for contributing to the overall excellent care of the patients and the data managers for assisting in the preparation of data for the paper. This work has been partly supported by grants from the Istituto Superiore di Sanità (National Program on Stem Cells), European Union (FP6 program ALLOSTEM), Regione Lombardia (Research Project: ‘Trapianto di cellule staminali adulte per scopi di terapia cellulare sostitutiva, riparativa e rigenerativa’), Fondazione CARIPLO to FL and the Dutch Program for Tissue Engineering.

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Author notes

  1. M E Bernardo and L M Ball: These authors contributed equally to this work.

  2. W E Fibbe and F Locatelli: These authors contributed equally to this work.

Authors and Affiliations

  1. Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

    M E Bernardo, A M Cometa, M Zecca, M A Avanzini, A Bertaina, L Vinti, R Maccario & F Locatelli

  2. Department of Pediatric Stem Cell Transplantation, Leiden University Medical Centre, Leiden, The Netherlands

    L M Ball, A Lankester & R M Egeler

  3. Department of Immunohematology and Stem Cell Research, Leiden University Medical Centre, Leiden, The Netherlands

    H Roelofs & W E Fibbe

  4. Division of Clinical Immunology and Center for Allogeneic Stem Cell Transplantation, Karolinska Institute, Huddinge University, Stockholm, Sweden

    O Ringden

  5. Division of Clinical Immunology and Transfusion Medicine, Karolinska Institute and Hematology Center, Karolinska Institute, Huddinge University, Stockholm, Sweden

    K Le Blanc

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  1. M E Bernardo
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Correspondence to M E Bernardo.

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Bernardo, M., Ball, L., Cometa, A. et al. Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation. Bone Marrow Transplant 46, 200–207 (2011). https://doi.org/10.1038/bmt.2010.87

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