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Advances in umbilical cord blood manipulation—from niche to bedside

Nature Reviews Clinical Oncology volume 12, pages 163–174 (2015)Cite this article

Subjects

Key Points

  • Umbilical cord blood (UCB) transplantation is limited by cell doses, especially for adult recipients

  • UCB can be expanded in vitro greater than 500-fold

  • UCB can be 'primed' just before infusion to influence cellular homing

  • Cell expansion or modulation of cell homing can alter engraftment kinetics in recipients

  • These strategies can increase the rapidity of engraftment and the next generation of clinical trials will determine the clinical efficacy of such approaches

Abstract

The use of umbilical cord blood (UCB) as an alternative haematopoietic cell source in lieu of bone marrow for haematopoietic reconstitution is increasingly becoming a mainstay treatment for both malignant and nonmalignant diseases, as most individuals will have at least one available, suitably HLA-matched unit of blood. The principal limitation of UCB is the low and finite number of haematopoietic stem and progenitor cells (HSPC) relative to the number found in a typical bone marrow or mobilized peripheral blood allograft, which leads to prolonged engraftment times. In an attempt to overcome this obstacle, strategies that are often based on native processes occurring in the bone marrow microenvironment or 'niche' have been developed with the goal of accelerating UCB engraftment. In broad terms, the two main approaches have been either to expand UCB HSPC ex vivo before transplantation, or to modulate HSPC functionality to increase the efficiency of HSPC homing to the bone marrow niche after transplant both of which enhance the biological activities of the engrafted HSPC. Several early phase clinical trials of these approaches have reported promising results.

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Figure 1: Median times to neutrophil engraftment of mobilized PBSC, unrelated donor marrow and single UCB transplants after a myeloablative preparative regimen (transplant is on day 0).
Figure 2: Activities of HSPC required for successful umbilical cord blood engraftment.
Figure 3: General schema of a double UCB transplant platform.
Figure 4: UCB manipulation offers improved time to neutrophil engraftment.

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Acknowledgements

The authors thank T. Glass for her conception and rendition of the bone-marrow microenvironment in Figure 2.

Author information

Authors and Affiliations

  1. Division of Pediatric Blood and Marrow Transplant, University of Minnesota, MMC 366, 420 Delaware Street SE, Minneapolis, 55445, MN, USA

    Troy C. Lund & John E. Wagner

  2. Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, 92121, CA, USA

    Anthony E. Boitano

  3. Fred Hutchinson Cancer Research Center, University of Washington, D2-100, 1100 Fairview Avenue North, Seattle, 98109, WA, USA

    Colleen S. Delaney

  4. The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit Number 423, Houston, 77030, TX, USA

    Elizabeth J. Shpall

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Contributions

T.C.L. researched data for article. A.E.B., C.S.D., E.J.S. and J.E.W. reviewed and edited the manuscript before submission. T.C.L. and J.E.W. substantially contributed to discussion of content. T.C.L. wrote the manuscript.

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Correspondence to Troy C. Lund.

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The authors declare no competing financial interests.

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Lund, T., Boitano, A., Delaney, C. et al. Advances in umbilical cord blood manipulation—from niche to bedside. Nat Rev Clin Oncol 12, 163–174 (2015). https://doi.org/10.1038/nrclinonc.2014.215

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