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Microencapsulation of parathyroid cells via electric field and non-surgical transplantation approach

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Abstract

Purpose

Hypoparathyroidism is a rare disease with low PTH, mostly seen as a consequence of neck surgery. Current management is the prescription of calcium and vitamin D, but the definitive treatment is parathyroid allotransplantation, which frequently triggers an immune response, thus cannot achieve the expected success. To overcome this problem, encapsulation of allogeneic cells is the most promising method. By optimizing the standard alginate cell encapsulation technique with parathyroid cells under high-voltage application, the authors reduced the size of parathyroid-encapsulated beads and evaluated these samples in vitro and in vivo.

Methods

Parathyroid cells were isolated, and standard-sized alginate macrobeads were prepared without any electrical field application, while microbeads in smaller sizes (< 500 µm), by the application of 13 kV. Bead morphologies, cell viability, and PTH secretion were evaluated in vitro for four weeks. For the in vivo part, beads were transplanted into Sprague–Dawley rats, and after retrieval, immunohistochemistry and PTH release were evaluated in addition to the assessment of cytokine/chemokine levels.

Results

The viability of parathyroid cells in micro- and macrobeads did not differ significantly. However, the amount of in vitro PTH secretion from microencapsulated cells was significantly lower than that from macroencapsulated cells, although it increased throughout the incubation period. Immunohistochemistry of PTH staining in both of the encapsulated cells identified as positive after retrieval.

Conclusion

Contrary to the literature, a minimal in vivo immune response was developed for alginate-encapsulated parathyroid cells, regardless of bead size. Our findings suggest that injectable, micro-sized beads obtained using high-voltage may be a promising method for a non-surgical transplantation approach.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. The data are not publicly available due to privacy or ethical restrictions.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, Istanbul Okan University, Tuzla, 34959, Istanbul, Türkiye

    Ö. Karabıyık Acar & G. D. Nozhatzadeh

  2. Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Ataşehir, 34755, Istanbul, Türkiye

    Ö. Karabıyık Acar, M. Keğin, G. D. Nozhatzadeh, A. A. Tuncer, F. Şahin & G. Torun Köse

  3. Department of Biophysics, Faculty of Medicine, Karadeniz Technical University, Ortahisar, 61080, Trabzon, Türkiye

    H. Başoğlu

  4. Department of General Surgery, GOP EAH, Health Science University, Gaziosmanpaşa, 34255, Istanbul, Türkiye

    M. Keğin

  5. Department of Pathology, Faculty of Medicine, Yeditepe University, Koşuyolu, 34718, Istanbul, Türkiye

    E. Hacıhasanoğlu

  6. Department of General Surgery, Faculty of Medicine, Yeditepe University, Koşuyolu, 34718, Istanbul, Türkiye

    E. Aysan

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  1. Ö. Karabıyık Acar
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Contributions

Conception and design of the study: EA, HB, GTK, FŞ and ÖKA. Acquisition of data: GDN, AAT, MK, EH and ÖKA. Analysis and interpretation of data: EA, GTK and ÖKA. Drafting or revising the manuscript: ÖKA, EA and GTK. All authors have approved the final article.

Corresponding author

Correspondence to Ö. Karabıyık Acar.

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Conflict of interest

The authors declare no competing interests.

Ethical approval

Human participants were treated in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Parathyroid tissues were obtained from the patients operated for subtotal parathyroidectomy for tertiary hyperparathyroidism.

Informed consent

Informed consent from the patients and the approval of the clinical studies ethical committee for the isolation of human cells (SBÜ Istanbul Training and Research Hospital, 11.07.2022, #217) were obtained. Rats were treated in accordance with the ethical guidelines of the National Research Council's Guide for the Care and Use of Laboratory Animals. Ethics committee approval was taken from Yeditepe University Local Ethics Committee for Animal Experiments (20.02.2021, 2021/01–5).

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Karabıyık Acar, Ö., Başoğlu, H., Keğin, M. et al. Microencapsulation of parathyroid cells via electric field and non-surgical transplantation approach. J Endocrinol Invest 46, 2257–2267 (2023). https://doi.org/10.1007/s40618-023-02075-7

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