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Multi-Spheroid-Loaded Human Acellular Dermal Matrix Carrier Preserves Its Spheroid Shape and Improves In Vivo Adipose-Derived Stem Cell Delivery and Engraftment

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Tissue Engineering and Regenerative Medicine Aims and scope

A Correction to this article was published on 28 July 2020

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Abstract

Background:

Current in vivo adult stem cell delivery presents limited clinical effects due to poor engraftment and survival. To overcome current challenges in cell delivery and promote surgical cell delivery for soft tissue repair, a multi-spheroid-loaded thin sectioned acellular dermal matrix (tsADM) carrier which preserves loaded spheroids’ three-dimensional (3D) structure, was developed.

Methods:

Adipose-derived stem cells (ASCs) were used for spheroid delivery. After generating spheroids in 3D cell culture dishes, spheroid plasticity and survival in-between coverslips were evaluated. Spheroids were loaded onto tsADM, their shape changes were followed up for 14 days, and then imaged. Spheroid adhesion stability to tsADM against shear stress was also evaluated. Finally, cell delivery efficacy was compared with cell-seeded tsADM by in vivo implantation and histological evaluation.

Results:

Spheroids withstood cyclic compression stress and maintained their 3D shape without fusion after 48 h of culture in-between coverslips. Cell survival improved when spheroids were cultured on tsADM in-between the coverslips. Spheroid-loaded tsADM with coverslips maintained their spheroid outline for 14 days of culture whereas without coverslips, the group lost their outline due to spreading after 4 days in culture. Spheroids loaded onto tsADMs were more stable after six rather than 3 days in culture. Spheroid-loaded tsADMs showed about a 2.96-fold higher ASCs transplantation efficacy than cell-seeded tsADMs after 2 weeks of in vivo transplantation.

Conclusion:

These results indicate that transplantation of spheroid-loaded tsADMs significantly improved cell delivery. These findings suggest that a combined approach with other cells, drugs, and nanoparticles may improve cell delivery and therapeutic efficacy.

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  • 28 July 2020

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2017R1C1B5017905). This research was supported by a Grant of Translational R&D Project through Institute for Bio-Medical convergence, Incheon St. Mary’s Hospital, The Catholic University of Korea

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Authors and Affiliations

  1. Department of Plastic and Reconstructive Surgery, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea

    Jie Hyun Kim & Jun Yong Lee

  2. Department of Plastic and Reconstructive Surgery, Incheon St. Mary′s Hospital, College of Medicine, The Catholic University of Korea, 56, Dongsu-ro, Bupyeong-gu, Incheon, 21431, Republic of Korea

    Jie Hyun Kim & Jun Yong Lee

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Contributions

JHK performed the experiments, analyzed the data and co-wrote the paper. JYL conceived of the presented idea, designed the study, performed the experiments, analyzed the data and wrote the manuscript.

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Correspondence to Jun Yong Lee.

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The authors declare that they have no conflict of interest.

Ethical statement

All in vivo experiments were carried out in accordance with the Institutional Animal Care and Use Committee (IACUC) of Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea (IACUC Approval No. 2019-008).

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Kim, J.H., Lee, J.Y. Multi-Spheroid-Loaded Human Acellular Dermal Matrix Carrier Preserves Its Spheroid Shape and Improves In Vivo Adipose-Derived Stem Cell Delivery and Engraftment. Tissue Eng Regen Med 17, 271–283 (2020). https://doi.org/10.1007/s13770-020-00252-w

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  • DOI: https://doi.org/10.1007/s13770-020-00252-w

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