International Journal of Molecular Sciences (Feb 2023)

Tissue-Oxygen-Adaptation of Bone Marrow-Derived Mesenchymal Stromal Cells Enhances Their Immunomodulatory and Pro-Angiogenic Capacity, Resulting in Accelerated Healing of Chemical Burns

  • Marina V. Volkova,
  • Ningfei Shen,
  • Anna Polyanskaya,
  • Xiaoli Qi,
  • Valery V. Boyarintsev,
  • Elena V. Kovaleva,
  • Alexander V. Trofimenko,
  • Gleb I. Filkov,
  • Alexandre V. Mezentsev,
  • Sergey P. Rybalkin,
  • Mikhail O. Durymanov

DOI
https://doi.org/10.3390/ijms24044102
Journal volume & issue
Vol. 24, no. 4
p. 4102

Abstract

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Transplantation of mesenchymal stromal cells (MSCs) provides a powerful tool for the management of multiple tissue injuries. However, poor survival of exogenous cells at the site of injury is a major complication that impairs MSC therapeutic efficacy. It has been found that tissue-oxygen adaptation or hypoxic pre-conditioning of MSCs could improve the healing process. Here, we investigated the effect of low oxygen tension on the regenerative potential of bone-marrow MSCs. It turned out that incubation of MSCs under a 5% oxygen atmosphere resulted in increased proliferative activity and enhanced expression of multiple cytokines and growth factors. Conditioned growth medium from low-oxygen-adapted MSCs modulated the pro-inflammatory activity of LPS-activated macrophages and stimulated tube formation by endotheliocytes to a much higher extent than conditioned medium from MSCs cultured in a 21% oxygen atmosphere. Moreover, we examined the regenerative potential of tissue-oxygen-adapted and normoxic MSCs in an alkali-burn injury model on mice. It has been revealed that tissue-oxygen adaptation of MSCs accelerated wound re-epithelialization and improved the tissue histology of the healed wounds in comparison with normoxic MSC-treated and non-treated wounds. Overall, this study suggests that MSC adaptation to ‘physiological hypoxia’ could be a promising approach for facilitating skin injuries, including chemical burns.

Keywords