Methods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications

doi:10.1586/17474086.2016.1128321

Review

. 2016 Mar;9(3):297-314.

doi: 10.1586/17474086.2016.1128321. Epub 2016 Jan 21.

Methods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications

Frédéric Baron^{1

2}, Annalisa Ruggeri^{3

4

5}, Arnon Nagler^{6

7

8

9}

Affiliations

¹ a Division of Hematology, Department of Medicine , University and CHU of Liège , Liège , Belgium.
² b GIGA-I3, Section of Hematology , University of Liège , Liège , Belgium.
³ c Eurocord Hospital Saint Louis, AP-HP , Paris , France.
⁴ d Hospital Saint Antoine , Service d'Hématologie et Thérapie Cellulaire, AP-HP , Paris , France.
⁵ e Cord Blood Committee, Cellular Therapy and Immunobiology Working Party , EBMT , Leiden , Netherlands.
⁶ f Division of Hematology and Bone Marrow Transplantation , The Chaim Sheba Medical Center, Tel-Hashomer , Ramat-Gan , Israel.
⁷ g EBMT Paris Office , Hospital Saint Antoine , Paris , France.
⁸ h Université Pierre et Marie Curie , Paris , France.
⁹ i Tel Aviv University (TAU) , Tel Aviv , Israel.

PMID: 26635058
DOI: 10.1586/17474086.2016.1128321

Review

Methods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications

Frédéric Baron et al. Expert Rev Hematol. 2016 Mar.

. 2016 Mar;9(3):297-314.

doi: 10.1586/17474086.2016.1128321. Epub 2016 Jan 21.

Authors

Frédéric Baron^{1

2}, Annalisa Ruggeri^{3

4

5}, Arnon Nagler^{6

7

8

9}

Affiliations

¹ a Division of Hematology, Department of Medicine , University and CHU of Liège , Liège , Belgium.
² b GIGA-I3, Section of Hematology , University of Liège , Liège , Belgium.
³ c Eurocord Hospital Saint Louis, AP-HP , Paris , France.
⁴ d Hospital Saint Antoine , Service d'Hématologie et Thérapie Cellulaire, AP-HP , Paris , France.
⁵ e Cord Blood Committee, Cellular Therapy and Immunobiology Working Party , EBMT , Leiden , Netherlands.
⁶ f Division of Hematology and Bone Marrow Transplantation , The Chaim Sheba Medical Center, Tel-Hashomer , Ramat-Gan , Israel.
⁷ g EBMT Paris Office , Hospital Saint Antoine , Paris , France.
⁸ h Université Pierre et Marie Curie , Paris , France.
⁹ i Tel Aviv University (TAU) , Tel Aviv , Israel.

PMID: 26635058
DOI: 10.1586/17474086.2016.1128321

Abstract

More than 40,000 unrelated cord blood transplantations (UCBT) have been performed worldwide as treatment for patients with malignant or non-malignant life threatening hematologic disorders. However, low absolute numbers of hematopoietic stem and progenitor cells (HSPCs) within a single cord blood unit has remained a limiting factor for this transplantation modality, particularly in adult recipients. Further, because UCB contains low numbers of mostly naïve T cells, immune recovery after UCBT is slow, predisposing patients to severe infections. Other causes of UCBT failure has included graft-versus-host disease (GVHD) and relapse of the underlying disease. In this article, we first review the current landscape of cord blood engineering aimed at improving engraftment. This includes approaches of UCB-HSPCs expansion and methods aimed at improving UCB-HSCPs homing. We then discuss recent approaches of cord blood engineering developed to prevent infection [generation of multivirus-specific cytotoxic T cells (VSTs) from UCB], relapse [transduction of UCB-T cells with tumor-specific chimeric receptor antigens (CARs)] and GVHD (expansion of regulatory T cells from UCB). Although many of these techniques of UCB engineering remain currently technically challenging and expensive, they are likely to revolutionize the field of UCBT in the next decades.

Keywords: HSPC; UCB; Umbilical cord blood; chimeric receptor antigen; cytotoxic T cells; engraftment; expansion; graft-versus-host disease; homing; regulatory T cells; transplantation.

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Methods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications

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Methods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications

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