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Cold Temperatures Provide a Boost for Cord Blood Stem Cell Transplantation

Review of “Enhanced collection of phenotypic and engrafting human cord blood hematopoietic stem cells at 4°C” from STEM CELLS by Stuart P. Atkinson

The lower number of hematopoietic stem cells (HSCs) present in cord blood samples, when compared with collections from the bone marrow or mobilized peripheral blood, represents a significant limitation to the implementation of this readily available resource in hematopoietic cell transplantation. Recent studies from Hal E. Broxmeyer and Maegan L. Capitano (Indiana University School of Medicine, Indianapolis, IN, USA) have explored various strategies to increase the number of HSCs in cord blood in the hope of improving hematopoietic cell transplantation outcomes. The use of hypoxia [1], hypoxia-mimetics [2], and combinations of antioxidants and/or epigenetic regulators [3] have all displayed promise in increasing HSC number in cord blood samples; however, each of these approaches entails significant limitations that have hampered their application.

As part of their ongoing quest, the Broxmeyer and Capitano teams recently evaluated the influence of temperature on the number of HSCs present in cord blood. Reporting in a recent STEM CELLS study [4], the authors now demonstrate that the collection and processing of cord blood under lower-than-normal temperatures enhances the numbers of phenotypically and functionally defined self‐renewing HSCs.

The team collected and processed freshly isolated human cord blood samples at 4°C, and, encouragingly, subsequent analysis revealed significantly higher numbers of defined phenotypic HSCs but no alterations to the number of multipotent progenitors or more mature progenitors. The authors also established an increase in the number of functional HSCs following cord blood collection at 4°C by demonstrating the increased engraftment of long‐term repopulating self‐renewing HSCs in sublethally irradiated immunodeficient mice. In agreement with previous studies using hypoxia [1], the increase in HSC numbers prompted a decrease in monoblast and myeloblast precursor cells and common myeloid progenitor cells, perhaps as a consequence of the blocked differentiation of HSCs.

The authors note the simplicity, clinical feasibility, cost-effectiveness, and lack of significant limitations of collecting cord blood in colder temperatures to enhance functional HSC numbers, and they anticipate that this approach may bypass the limitations associated with cord blood use in hematopoietic cell transplantation.

For more on enhanced techniques that can boost HSC numbers and improve cord blood hematopoietic cell transplantation-based approaches, stay tuned to the Stem Cells Portal!


  1. Mantel Charlie R, O’Leary Heather A, Chitteti Brahmananda R, et al., Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock. Cell 2015;161:1553-1565.
  2. Broxmeyer HE, O’Leary HA, Huang X, et al., The importance of hypoxia and extra physiologic oxygen shock/stress for collection and processing of stem and progenitor cells to understand true physiology/pathology of these cells ex vivo. Current Opinion in Hematology 2015;22.
  3. Cai Q, Capitano M, Huang X, et al., Combinations of antioxidants and/or of epigenetic enzyme inhibitors allow for enhanced collection of mouse bone marrow hematopoietic stem cells in ambient air. Blood Cells, Molecules, and Diseases 2018;71:23-28.
  4. Broxmeyer HE, Cooper S, and Capitano ML, Enhanced collection of phenotypic and engrafting human cord blood hematopoietic stem cells at 4°C. STEM CELLS 2020;38:1326-1331.