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Effects of chitosan-glycerol phosphate hydrogel on the maintenance and homing of hAd-MSCs after xenotransplantation into the rat liver

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Abstract

Problems associated with the treatment of liver failure necessitate more research on advanced strategies like cell-based therapy and tissue engineering. Since cell therapy approaches suffer from some limitations, tissue engineering and material science converge the sight onto stem cell-biomaterial based therapy. In this study, the human adipose-derived mesenchymal stem cells (hAd-MSCs), carrying ectopic fluorescent reporter genes, were encapsulated in the chitosan-β-glycerol phosphate hydroxyethyl cellulose (β-GP-HEC) and transplanted into the right lobe of the intact liver of Wistar rats (as cell-laden scaffolds). In addition, labeled hAd-MSCs were injected into the liver (as scaffold-free groups). All experimental groups were monitored after 15, 45, 90, and 180 days of transplantation. Fluorescence microscopy and histological evaluations were used to monitor the migration and distribution of cells within the two test groups along with their related controls, during the 6-month follow-up. Moreover, the ability of cells to migrate to other tissues was detected by quantitative PCR. Macroscopic inspection during this period showed no evidence of pathological inflammatory responses. Microscopic observations revealed that the injected cells were detectable at the target organ, for at least 6 months in both scaffold and scaffold-free groups. However, the scaffold-free samples showed signs of reduction in cellular augmentation over time. The molecular assessment also confirmed that the application of scaffold in vivo reduced unnecessary cell migration into other organs. In conclusion, the application of cell-seeded β-GP-HEC scaffold not only improved cell survival but also reduced the rate of cellular escape from the target area of transplantation.

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Acknowledgements

The authors thank Ehsan Bahramzadeh and Mohammadmahdi Esmail-Jami for their editing suggestions, as well as Hassan Tamadonipour, Mohammad Nakhaei, and Dr. Moein Farschian for their excellent technical assistance.

Funding

The study was financed by grants from Ferdowsi University of Mashhad and Iran National Science Foundation (INSF) and performed in the Institute of Biotechnology, Ferdowsi University of Mashhad.

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Authors and Affiliations

  1. Industrial Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

    Aliakbar Haddad-Mashadrizeh, Shabnam Ensandost & Ahmad Reza Bahrami

  2. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

    Maryam M. Matin & Ahmad Reza Bahrami

  3. Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

    Maryam M. Matin

  4. National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran

    Fahimeh Shahabipour

  5. Skin Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran

    Fahimeh Shahabipour

  6. National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

    Alireza Zomorodipour

Authors
  1. Aliakbar Haddad-Mashadrizeh
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  2. Maryam M. Matin
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  3. Fahimeh Shahabipour
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  4. Shabnam Ensandost
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  5. Alireza Zomorodipour
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  6. Ahmad Reza Bahrami
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Contributions

AHM, MMM, and ARB were responsible for the design of experiments and data acquisition, and data interpretation; FS, SE, and AZ contributed to data analysis and manuscript preparation. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Ahmad Reza Bahrami.

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The authors declare that the research was conducted with the approval from Ferdowsi University of Mashhad Ethics Committee (IR.UM.REC.1399.069). Written informed consents were obtained from the patients.

Conflict of interest

The authors declare no competing interests.

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Haddad-Mashadrizeh, A., Matin, M.M., Shahabipour, F. et al. Effects of chitosan-glycerol phosphate hydrogel on the maintenance and homing of hAd-MSCs after xenotransplantation into the rat liver. emergent mater. 5, 519–528 (2022). https://doi.org/10.1007/s42247-021-00167-9

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  • DOI: https://doi.org/10.1007/s42247-021-00167-9

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