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CD14 positive cells accelerate hematopoietic stem cell engraftment

Bone Marrow Transplantation volume 57, pages 942–948 (2022)Cite this article

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Abstract

The improvement of hematopoietic stem and progenitor cell (HSPC) engraftment remains a high-priority goal when limited cell doses are available, such as in cord blood (CB) transplantation and HSC gene therapy. We observed that monocytes are highly effective at improving the engraftment of both CB-CD34+ and lentivirus-transfected CD34+ cells in a xenogeneic model of HSC transplantation. Moreover, monocytes, in particular the CD14+CD16− classical subset, in co-culture systems increase survival and stemness of CB-CD34+ cells. Both soluble factors and direct-cell contact interactions, such as JAG/NOTCH and COX-2/PGE2 pathways, are critically involved in the HSC-monocyte crosstalk. Our results indicate that the infusion of monocytes improves engraftment when cell dose is a limiting factor.

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Fig. 1: Human CD14+ monocytes expedite in vivo engraftment of CB-CD34+ cells and of lentiviral transduced CD34+ cell and increase their survival and stemness in vitro.
Fig. 2: Classical monocytes positively influence CB-CD34+ cell survival and stemness throught JAG1/NOTCH and COX-2/PGE2 pathways.

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The authors declare that all data supporting the findings of this study are available within the article and its supplementary information files.

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Acknowledgements

We would like to thank Fondazione Matilde Tettamanti, Comitato Maria Letizia Verga, and Fondazione MBBM for their generous support. This work was supported by Blood Cancer UK.

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Author notes

  1. These authors contributed equally: Alice Pievani, Valentina Granata, Francesco Dazzi, Marta Serafini.

Authors and Affiliations

  1. Centro Ricerca M. Tettamanti, Department of Pediatrics, University of Milano-Bicocca, Monza, Italy

    Alice Pievani, Valentina Granata & Marta Serafini

  2. School of Cancer and Pharmacological Sciences and KHP Cancer Research UK Centre, King’s College London, London, UK

    Alice Pievani, Antonio Galleu & Francesco Dazzi

  3. San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy

    Giacomo Desantis & Bernhard Gentner

  4. Centro di Biostatistica per l’epidemiologia clinica, Department of Health Sciences, University of Milano-Bicocca, Monza, Italy

    Laura Antolini

  5. Department of Obstetrics and Gynecology, Fondazione MBBM, University of Milano-Bicocca, Monza, Italy

    Sara Ornaghi

  6. Department of Pediatrics, Pediatric Hematology-Oncology Unit, Fondazione MBBM/San Gerardo Hospital, Monza, Italy

    Andrea Biondi

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  1. Alice Pievani
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Contributions

AP and VG collection and assembly of data, data analysis and interpretation, manuscript writing; GD collection and assembly of data; LA statistical analysis; SO provision of study material or patients; BG, AG, and AB manuscript reviewing and editing; FD and MS conception and design, manuscript writing and final approval of manuscript.

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Correspondence to Francesco Dazzi or Marta Serafini.

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Pievani, A., Granata, V., Desantis, G. et al. CD14 positive cells accelerate hematopoietic stem cell engraftment. Bone Marrow Transplant 57, 942–948 (2022). https://doi.org/10.1038/s41409-022-01662-1

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