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Exosomes derived from human adipose mesenchymal stem cells loaded bioengineered three-dimensional amniotic membrane-scaffold-accelerated diabetic wound healing

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Abstract

The occurrence of wounds and defects in the healing process is one of the main challenges in diabetic patients. Herein, we investigated whether adipose-derived stem cells (ADSCs)-derived exosomes loaded bioengineered micro-porous three-dimensional amniotic membrane-scaffold (AMS) could promote healing in diabetic rats. Sixty diabetic rats were randomly allocated into the control group, exosome group, AMS group, and AMS + Exo group. On days 7, 14, and 21, five rats from each group were sampled for stereological, immunohistochemical, molecular, and tensiometrical assessments. Our results indicated that the wound closure rate, the total volumes of newly formed epidermis and dermis, the numerical densities of fibroblasts and proliferating cells, the length density blood vessels, collagen density as well as tensiometrical parameters of the healed wounds were considerably greater in the treated groups than in the control group, and these changes were more obvious in the AMS + Exo ones. Furthermore, the expression of TGF-β, bFGF, and VEGF genes was meaningfully upregulated in all treated groups compared to the control group and were greater in the AMS + Exo group. This is while expression of TNF-α and IL-1β, as well as cell numerical densities of neutrophils, M1 macrophages, and mast cells decreased more considerably in the AMS + Exo group in comparison with the other groups. Generally, it was found that using both AMS transplantation and ADSCs-derived exosomes has more effect on diabetic wound healing.

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The data that support the findings of this study are available from the corresponding authors upon reasonable request.

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Acknowledgements

We would like to express our appreciation to Prof. Abbas Piryaei for his cooperation and technical support.

Funding

The current project was financially supported by grants to D. N. from Mazandaran University of Medical Sciences (Grant No.13758), Sari, Iran.

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Authors and Affiliations

  1. Cellular and Molecular Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Ali Reza Khalatbary

  2. Health Reproductive Research Center, Islamic Azad University, Sari, Iran

    Melody Omraninava

  3. Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran

    Davood Nasiry

  4. Eye Research Center, Eye Department, Amiralmomenin Hospital, School of Medicine, Guilan University of Medical Science, Rasht, Iran

    Mitra Akbari

  5. Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Saeid Taghiloo

  6. Department of Artificial Intelligence, Smart University of Medical Sciences, Tehran, Iran

    Mahnaz Poorhassan

  7. Department of Anatomical Sciences, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Roohollah Ebrahimpour-Malekshah

  8. Department of Anatomical Sciences, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahdiyeh Asadzadeh

  9. Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Amir Raoofi

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Contributions

A.R.K. contributed to the study design, data acquisition, and analysis, as well as drafting of the manuscript. M.O. contributed to the study design and fabrication of AMS and characterization. M.P. and M.As. contributed to isolation and characterization of ADSCs-derived exosomes. S.T. designed molecular assessments and analyses. R.E-M. designed tensiometrical tests, and contributed to acquisition and analysis of the data. D.N. supervised the study, provided financial support, and contributed to the study concept and design, interpretation of data, and editing and final approval of the manuscript. M.Ak. provided financial support, interpretation of data, and editing and final approval of the manuscript. A.R. designed stereological assessments and analyses. All authors reviewed and commented on the manuscript and approved the final manuscript.

Corresponding authors

Correspondence to Davood Nasiry or Mitra Akbari.

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The authors declare no competing interests.

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The authors declare no conflicts of interest.

Ethical approval

The written informed consent was obtained before clinical sampling of the AM and adipose tissue. The use of the AM samples and laboratory animals was approved by the Ethics Committee of Mazandaran University of Medical Sciences (Ethic code: IR.MAZUMS.4.REC.1400.13758). Methods were performed according to ARRIVE guidelines.

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Khalatbary, A.R., Omraninava, M., Nasiry, D. et al. Exosomes derived from human adipose mesenchymal stem cells loaded bioengineered three-dimensional amniotic membrane-scaffold-accelerated diabetic wound healing. Arch Dermatol Res 315, 2853–2870 (2023). https://doi.org/10.1007/s00403-023-02709-z

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