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Hydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands

Author

Listed:
  • Y. Wang

    (Australian National University
    The University of Melbourne
    The University of Melbourne)

  • E. R. Zoneff

    (Australian National University
    The University of Melbourne)

  • J. W. Thomas

    (Australian National University)

  • N. Hong

    (Australian National University)

  • L. L. Tan

    (Australian National University)

  • D. J. McGillivray

    (University of Auckland)

  • A. W. Perriman

    (Australian National University
    University of Bristol, Bristol)

  • K. C. L. Law

    (The Florey Institute of Neuroscience and Mental Health, The University of Melbourne)

  • L. H. Thompson

    (The Florey Institute of Neuroscience and Mental Health, The University of Melbourne)

  • N. Moriarty

    (The Florey Institute of Neuroscience and Mental Health, The University of Melbourne)

  • C. L. Parish

    (The Florey Institute of Neuroscience and Mental Health, The University of Melbourne)

  • R. J. Williams

    (Deakin University)

  • C. J. Jackson

    (Australian National University
    Australian National University
    Australian National University)

  • D. R. Nisbet

    (Australian National University
    The University of Melbourne
    The University of Melbourne)

Abstract

Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.

Suggested Citation

  • Y. Wang & E. R. Zoneff & J. W. Thomas & N. Hong & L. L. Tan & D. J. McGillivray & A. W. Perriman & K. C. L. Law & L. H. Thompson & N. Moriarty & C. L. Parish & R. J. Williams & C. J. Jackson & D. R. N, 2023. "Hydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36133-8
    DOI: 10.1038/s41467-023-36133-8
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    References listed on IDEAS

    as
    1. Christopher M. Madl & Sarah C. Heilshorn & Helen M. Blau, 2018. "Bioengineering strategies to accelerate stem cell therapeutics," Nature, Nature, vol. 557(7705), pages 335-342, May.
    2. Thorsten Burmester & Bettina Weich & Sigrid Reinhardt & Thomas Hankeln, 2000. "A vertebrate globin expressed in the brain," Nature, Nature, vol. 407(6803), pages 520-523, September.
    3. Maria J. Rodríguez-Colman & Matthias Schewe & Maaike Meerlo & Edwin Stigter & Johan Gerrits & Mia Pras-Raves & Andrea Sacchetti & Marten Hornsveld & Koen C. Oost & Hugo J. Snippert & Nanda Verhoeven-D, 2017. "Interplay between metabolic identities in the intestinal crypt supports stem cell function," Nature, Nature, vol. 543(7645), pages 424-427, March.
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