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Improvement of damaged cavernosa followed by neuron-like differentiation at injured cavernous nerve after transplantation of stem cells seeded on the PLA nanofiber in rats with cavernous nerve injury

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Abstract

This study investigated the differentiation of transplanted transplanted mesenchymal stem cells MSCs into neuron-like cells, repair of erectile dysfunction (ED), and synergy of MSCs seeded to nanofibrous scaffolds with after transplantation around the injured cavernous nerve (CN) of rats. The synthesized polymer was electrospun in a rotating drum to prepare nanofiber meshes (NMs). Human MSCs were prepared and confirmed. Eight-week-old male Sprague–Dawley rats were divided into five groups of six each: group 1—sham operation; group 2—CN injury; group 3—MSCs treatment after CN injury; group 4—nanofibrous scaffold treatment after CN injury; and group 5—post-CN injury treatment combining a nanofibrous scaffold and MSCs (nano-MSCs). In the latter group, the damaged CN was instantly surrounded by an MSC-containing a nanofibrous scaffold in the aftermath of injury. Morphological analysis and immuno-histochemical staining in relation to nerves (Tuj1, NF, MAP2, MBP and peripherin), endothelium (vWF), smooth muscle (SMA), neurofilament (NF), and apoptosis (TUNEL) were performed. We evaluated the mean proportion expressed as a percentage of the ratio of muscle to collagen of penile cavernous smooth-muscle cells as well as the expression of cavernous SMA, NF, vWF, and TUNEL makers. Compared to the group free of CN injury, erectile function was markedly reduced in the group with CN injury at 2 and 4 weeks (p < 0.05). By contrast, compared to the sham operation group, erectile function was better in the group with MSC transplantation (p < 0.05). Similarly, by comparison to the group solely with hMSCs, erectile function was better in the group with nano-MSC transplantation (p < 0.05). Transplantation of MSCs demonstrated the neuronal differentiation. By contrast to MSCs on their own, neuronal differentiation was more significantly expressed in nano-MSCs. The mean proportion expressed as a percentage of the ratio of muscle to collagen of penile cavernous smooth-muscle cells, the expression of cavernous SMA, NF, vWF, and apoptosis improved in the cavernosum after transplantation. NMs showed synergy with MSCs for the repair of erectile dysfunction. Transplanted MSCs differentiated into neuron-like cells and repaired erectile dysfunction in the rats with CN injury. Transplanted MSCs increased the mean percentage of the collagen area of the caversnosum as well as the expression levels of cavernous neuronal, endothelial, smooth-muscle markers, and apoptosis.

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Acknowledgements

This research was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2015R1D1A1A01056951), and Soonchunhyang University Research Fund.

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Authors and Affiliations

  1. Department of Urology, Soonchunhyang University School of Medicine, Seoul, Republic of Korea

    Jae Heon Kim & Yun Seob Song

  2. Department of Microbiology, Soonchunhyang University School of Medicine, Cheonan, Republic of Korea

    Jae Heon Kim

  3. Department of Urology, Soonchunhyang University School of Medicine, Gumi, Republic of Korea

    Jong Hyun Yun

  4. Korea Medical Dispute Mediation and Abitration Agency, Seoul, Republic of Korea

    Eun Seop Song

  5. Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada

    Seung U. Kim

  6. College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea

    Hong Jun Lee

  7. Research Institute, e-Biogen Inc, Seoul, Republic of Korea

    Hong Jun Lee

Authors
  1. Jae Heon Kim
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  2. Jong Hyun Yun
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  3. Eun Seop Song
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  4. Seung U. Kim
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Contributions

Conceived and designed the experiments: HJL, SUK, YSS. Performed the experiments: JHK, JHY, ESS. Analyzed the data: JHK, HJL, YSS. Wrote the paper: JHK, HJL, YSS.

Corresponding authors

Correspondence to Hong Jun Lee or Yun Seob Song.

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The authors declare that there are no conflicts of interest regarding the publication of this paper.

Ethical approval

This experiment was approved by the Institutional Animal Care and Use Committee of Soonchunhyang University Seoul Hospital.

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Kim, J.H., Yun, J.H., Song, E.S. et al. Improvement of damaged cavernosa followed by neuron-like differentiation at injured cavernous nerve after transplantation of stem cells seeded on the PLA nanofiber in rats with cavernous nerve injury. Mol Biol Rep 48, 3549–3559 (2021). https://doi.org/10.1007/s11033-021-06332-x

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  • DOI: https://doi.org/10.1007/s11033-021-06332-x

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