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New aspects of HSC mobilization for better therapeutic outcomes

Cellular & Molecular Immunology volume 18, pages 2583–2585 (2021)Cite this article

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Various agents have been characterized and are in clinical use to increase the yield of HSCs by inducing their mobilization from the bone marrow (BM) niche. Prominent among these agents are granulocyte colony-stimulating factor (G-CSF), agonists and antagonists of various chemokines, signaling molecules involved in HSC homing and retention in the BM, inputs from HSC niche cells, and inputs from the nervous system [3,4,5]. Studies in murine models and humans have revealed a significant increase in the number of phenotypic HSCs (Lin-Sca-1+c-Kit+CD48-; LSKCD48- cells in mice and Lin-CD34+ cells in humans) in the blood circulation following treatment with these agents, which could be used for therapeutic purposes [6, 7]. However, while we have devised some procedures to increase HSC yields, we still do not understand the detailed underlying mechanisms that facilitate increased HSC mobilization from the BM to the blood circulation [8,9,10]. Whether G-CSF and other factors work in a coordinated manner or there are distinct mechanisms associated with each of these agents to mobilize HSCs is important to explore, as this will help in reducing unintended side effects and will streamline the process of improving the yield and therapeutic success. In a recent issue of the journal Nature, Gao et al. described that in the BM, inputs from nociceptive nerves, which are generally involved in pain perception in tissues exposed to the external environment, such as skin, lung, and gut, have distinct and sustained effects on mobilizing HSCs [2]. This interesting study further delineates that certain components of the spices we use in our food can in fact stimulate HSC mobilization and could be of potential therapeutic importance.

To determine the extent of the contribution of nociceptive nerves in the HSC niche, the authors evaluated the abundance of these neurons in normal mouse BM and found that these nerves, characterized by their expression of the molecule ‘calcitonin gene-related peptide’ (CGRP) occupy  a far larger area in the BM than sympathetic neurons that express the enzyme tyrosine hydroxylase (TH). Ablating the inputs from nociceptive and sympathetic nerves individually or in combination with selective chemical inhibitors (resiniferatoxin (RTX) and 6-hydroxydopamine (6OHDA), respectively) revealed that HSC physiology was severely altered only in the context of combined ablation. However, ablation induced HSC expansion and had no impact on HSC homing to the BM, while their long-term reconstitution capacity was strongly reduced. Using a genetically manipulated mouse model to ablate these neural inputs, the authors confirmed a similar defect in HSCs, suggesting that these different branches of the nervous system provide distinct inputs to maintain HSCs in their niche [2].

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References

  1. Bensinger W, DiPersio JF, McCarty JM. Bone Marrow Transpl. 2009;43:181–95.

    Article  CAS  Google Scholar 

  2. Gao X, Zhang D, Xu C, Li H, Caron KM, Frenette PS. Nature. 2021;589:591–6.

    Article  CAS  Google Scholar 

  3. Bendall LJ, Bradstock KF. Cytokine Growth Factor Rev. 2014;25:355–67.

    Article  CAS  Google Scholar 

  4. Winkler IG, Levesque JP. Exp Hematol. 2006;34:996–1009.

    Article  CAS  Google Scholar 

  5. Katayama Y, Battista M, Kao WM, Hidalgo A, Peired AJ, Thomas SA, et al. Cell. 2006;124:407–21.

    Article  CAS  Google Scholar 

  6. Abkowitz JL, Robinson AE, Kale S, Long MW, Chen J. Blood. 2003;102:1249–53.

    Article  CAS  Google Scholar 

  7. Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA, et al. J Exp Med. 2005;201:1307–18.

    Article  CAS  Google Scholar 

  8. Halter J, Kodera Y, Ispizua AU, Greinix HT, Schmitz N, Favre G, et al. Haematologica. 2009;94:94–101.

    Article  Google Scholar 

  9. Hölig K, Kramer M, Kroschinsky F, Bornhäuser M, Mengling T, Schmidt AH, et al. Blood. 2009;114:3757–63.

    Article  Google Scholar 

  10. D’Souza A, Jaiyesimi I, Trainor L, Venuturumili P. Transfus Med Rev. 2008;22:280–90.

    Article  Google Scholar 

  11. Suekane A, Saito Y, Nakahata S, Ichikawa T, Ogoh H, Tsujikawa K, et al. Sci Rep. 2019;9:429.

    Article  Google Scholar 

  12. Christopher MJ, Rao M, Liu F, Woloszynek JR, Link DC. J Exp Med. 2011;208:251–60.

    Article  CAS  Google Scholar 

  13. Winkler IG, Sims NA, Pettit AR, Barbier V, Nowlan B, Helwani F, et al. Blood. 2010;116:4815–28.

    Article  CAS  Google Scholar 

  14. Adams GB, Alley IR, Chung UI, Chabner KT, Jeanson NT, Lo Celso C, et al. Nature. 2009;459:103–7.

    Article  CAS  Google Scholar 

  15. Villalón L, Odriozola J, Laraña JG, Zamora C, Pérez de Oteyza J, Jodra MH, et al. Hematol J. 2000;1:374–81.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by a Fellowship from the Vandervell Foundation, UK to AP.

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  1. Peninsula School of Medicine, Faculty of Health, University of Plymouth, Plymouth, UK

    Amiya K. Patra

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Correspondence to Amiya K. Patra.

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Patra, A.K. New aspects of HSC mobilization for better therapeutic outcomes. Cell Mol Immunol 18, 2583–2585 (2021). https://doi.org/10.1038/s41423-021-00723-7

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