Fully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to G(ALERT)

Lee, Geoffrey, Espirito Santo, Ana Isabel, Zwingenberger, Stefan, Cai, Lawrence, Vogl, Thomas, Feldmann, Marc, Horwood, Nicole J, Chan, James K and Nanchahal, Jagdeep (2018) Fully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to G(ALERT). Proceedings of the National Academy of Sciences of the United States of America (PNAS), 115 (19). E4463-E4472. ISSN 1091-6490

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Abstract

A major discovery of recent decades has been the existence of stem cells and their potential to repair many, if not most, tissues. With the aging population, many attempts have been made to use exogenous stem cells to promote tissue repair, so far with limited success. An alternative approach, which may be more effective and far less costly, is to promote tissue regeneration by targeting endogenous stem cells. However, ways of enhancing endogenous stem cell function remain poorly defined. Injury leads to the release of danger signals which are known to modulate the immune response, but their role in stem cell-mediated repair in vivo remains to be clarified. Here we show that high mobility group box 1 (HMGB1) is released following fracture in both humans and mice, forms a heterocomplex with CXCL12, and acts via CXCR4 to accelerate skeletal, hematopoietic, and muscle regeneration in vivo. Pretreatment with HMGB1 2 wk before injury also accelerated tissue regeneration, indicating an acquired proregenerative signature. HMGB1 led to sustained increase in cell cycling in vivo, and using Hmgb1 -/- mice we identified the underlying mechanism as the transition of multiple quiescent stem cells from G0 to GAlert HMGB1 also transitions human stem and progenitor cells to GAlert Therefore, exogenous HMGB1 may benefit patients in many clinical scenarios, including trauma, chemotherapy, and elective surgery.

Item Type: Article
Additional Information: Copyright © 2018 the Author(s). Published by PNAS.
Uncontrolled Keywords: animals,cell cycle,cells, cultured,metabolism,therapy,physiology,cytology,humans,mice,mice, knockout,cytology,osteogenesis,metabolism,regeneration,signal transduction,wound healing
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 06 Mar 2019 11:30
Last Modified: 05 Oct 2020 23:52
URI: https://ueaeprints.uea.ac.uk/id/eprint/70158
DOI: 10.1073/pnas.1802893115

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