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Synergistic Effect of Human Chorionic Gonadotropin and Granulocyte Colony Stimulating Factor in the Mobilization of HSPCs Improves Overall Survival After PBSCT in a Preclinical Murine Model. Are We Far Enough for Therapy?

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Abstract

Strategies to improve hematopoietic stem and progenitor cell (HSPC) mobilization from the bone marrow can have a pivotal role in addressing iatrogenic bone-marrow insufficiency from chemo(radio)therapy and overcoming peripheral blood stem cell transplantation (PBSCT) limitations such as insufficient mobilization. Granulocyte-colony stimulating factor (G-CSF) represents the standard mobilization strategy for HSPC and has done so for more than three decades since its FDA approval. Its association with non–G-CSF agents is often employed for difficult HSPC mobilization. However, obtaining a synergistic effect between the two classes is limited by different timing and mechanisms of action. Based on our previous in vitro results, we tested the mobilization potential of human chorionic gonadotropin (HCG), alone and in combination with G-CSF in vivo in a murine study. Our results show an improved mobilization capability of the combination, which seems to act synergistically in stimulating hematopoiesis. With the current understanding of the dynamics of HSPCs and their origins in more primitive cells related to the germline, new strategies to employ the mobilization of hematopoietic progenitors using chorionic gonadotropins could soon become clinical practice.

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Data Availability

The data supporting this study's findings are available from the corresponding author, [CCA], upon reasonable request.

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This work was supported by the national grant PN-III-P1-1.1-PD-2019–1095, PD 202 ⁄ 2020 TROFOSTEM “Evaluation of the effect of human chorionic gonadotropin in stem cell transplantation as a novel approach for pretransplant mobilization”.

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Authors and Affiliations

  1. Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu”, University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, P.O. 400393, Cluj-Napoca, Romania

    Cosmin Andrei Cismaru, Ancuta Jurj, Sergiu Chira, Ekaterina Isachekcu & Ioana Berindan Neagoe

  2. MEDFUTURE - The Research Center for Advanced Medicine “Iuliu Hatieganu”, University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Ciprian Tomuleasa, Diana Gulei & Raluca Munteanu

  3. Department of Internal Medicine, Cardiology-Rehabilitation, “Iuliu Hatieganu”, University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Gabriel Cismaru

  4. Laboratory Animal Facility - Centre for Experimental Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Luciana Madalina Gherman

Authors
  1. Cosmin Andrei Cismaru
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  2. Ciprian Tomuleasa
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  3. Ancuta Jurj
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  4. Sergiu Chira
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  5. Ekaterina Isachekcu
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  6. Gabriel Cismaru
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  7. Luciana Madalina Gherman
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  8. Diana Gulei
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  9. Raluca Munteanu
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  10. Ioana Berindan Neagoe
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Contributions

CCA- study design and writing of the manuscript. TC- study coordination. JA- immunophenotyping. CS- manuscript revision. IE- sample processing. CG- data curation. GLM, GD and MR- animal experiments. BNI- critical revision for important intellectual content.

Corresponding author

Correspondence to Cosmin Andrei Cismaru.

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Ethics Approval

The study was approved by the ethics committee of the University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca, Romania with the approval no. 27/21.02.2023 and the National Sanitary Veterinary and Food Safety Agency of Romania with the approval no. 359/24.03.2023.

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The authors have no competing interests to declare that are relevant to the content of this article.

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Cismaru, C.A., Tomuleasa, C., Jurj, A. et al. Synergistic Effect of Human Chorionic Gonadotropin and Granulocyte Colony Stimulating Factor in the Mobilization of HSPCs Improves Overall Survival After PBSCT in a Preclinical Murine Model. Are We Far Enough for Therapy?. Stem Cell Rev and Rep 20, 206–217 (2024). https://doi.org/10.1007/s12015-023-10648-5

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