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

• Published in: International journal of molecular sciences 2023-02, Vol.24 (4), p.4102
• Main Authors: Volkova, Marina V, Shen, Ningfei, Polyanskaya, Anna, Qi, Xiaoli, Boyarintsev, Valery V, Kovaleva, Elena V, Trofimenko, Alexander V, Filkov, Gleb I, Mezentsev, Alexandre V, Rybalkin, Sergey P, Durymanov, Mikhail O
• Format: Article
• Language: English
• Subjects: Adaptation; Analysis; Angiogenesis; Animals; Atmosphere; Bone Marrow; burn model; Burns; Burns, Chemical; Burns, Chemical - metabolism; Cell cycle; cellular respiration; Conditioning; Cytokines; Fibroblasts; Flow cytometry; Gene expression; Growth factors; Healing; Health aspects; Histology; Hypoxia; Hypoxia - metabolism; Immunomodulation; Inflammation; Influence; Injuries; injury; Macrophages; mesenchymal stem cell; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; Morphology; Oxidative stress; Oxygen - metabolism; Oxygen tension; Physiological aspects; Preconditioning; Skin; Skin injuries; Stem cells; Stromal cells; Tissue engineering; Transplantation; Wound Healing; Wounds
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24044102

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.