Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve Injury

The main cause of erectile dysfunction (ED) is the damage in penile cavernous endothelial cells (EC). Murine primary ECs have a limited growth potential, and the easy availability of murine ECs will facilitate the study of cavernous endothelial dysfunction in rats. This study was performed to establ...

Full description

Bibliographic Details
Main Authors: Sang Hong Bak, Jae Heon Kim, Seung U. Kim, Dong-Seok Lee, Yun Seob Song, Hong J. Lee
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/16/1/123
_version_ 1797437840933519360
author Sang Hong Bak
Jae Heon Kim
Seung U. Kim
Dong-Seok Lee
Yun Seob Song
Hong J. Lee
author_facet Sang Hong Bak
Jae Heon Kim
Seung U. Kim
Dong-Seok Lee
Yun Seob Song
Hong J. Lee
author_sort Sang Hong Bak
collection DOAJ
description The main cause of erectile dysfunction (ED) is the damage in penile cavernous endothelial cells (EC). Murine primary ECs have a limited growth potential, and the easy availability of murine ECs will facilitate the study of cavernous endothelial dysfunction in rats. This study was performed to establish immortalized rat penile cavernous ECs (rEC) and investigate how they could repair erectile dysfunction in rats with cavernous nerve injury (CNI). rEC was isolated enzymatically by collagenase digestion and were cultured. An amphotropic replication-incompetent retroviral vector encoding <i>v-myc</i> oncogene was used to transfect rEC for immortalization (vREC). Morphological and immunohistochemical properties of vREC were examined. Eight-week-old male Sprague-Dawley rats were divided into three groups of five rats each, including group 1 = sham operation, group 2 = bilateral CN injury, group 3 = vREC (1 × 10<sup>6</sup> cells) treatment after CNI. Erectile response was assessed at 2, 4 weeks after transplantation of vREC., Penile tissue were harvested at 4 weeks after transplantation and immune–histochemical examination was performed. vREC showed the expression of CD31, vWF, cell type-specific markers for EC by RT-PCR and flowcytometry. At 2, 4 weeks after transplantation, rats with CNI had significantly lower erectile function than control group (<i>p</i> < 0.05). The group transplanted with vREC showed higher erectile function than the group without vRECs (<i>p</i> < 0.05). vREC was established and repaired erectile dysfunction in rats with CNI. This cell line may be useful for studying mechanisms and drug screening of erectile dysfunction of rats.
first_indexed 2024-03-09T11:28:28Z
format Article
id doaj.art-66a4990867694dcbb1ee4614d6add4b4
institution Directory Open Access Journal
issn 1424-8247
language English
last_indexed 2024-03-09T11:28:28Z
publishDate 2023-01-01
publisher MDPI AG
record_format Article
series Pharmaceuticals
spelling doaj.art-66a4990867694dcbb1ee4614d6add4b42023-11-30T23:56:07ZengMDPI AGPharmaceuticals1424-82472023-01-0116112310.3390/ph16010123Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve InjurySang Hong Bak0Jae Heon Kim1Seung U. Kim2Dong-Seok Lee3Yun Seob Song4Hong J. Lee5Research Institute, Humetacell Inc., Bucheon 14786, Gyeonggi, Republic of KoreaDepartment of Urology, Soonchunhyang University School of Medicine, Seoul 04401, Republic of KoreaDivision of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, BC V6T 2B5, CanadaBK21 Plus KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaDepartment of Urology, Soonchunhyang University School of Medicine, Seoul 04401, Republic of KoreaResearch Institute, Humetacell Inc., Bucheon 14786, Gyeonggi, Republic of KoreaThe main cause of erectile dysfunction (ED) is the damage in penile cavernous endothelial cells (EC). Murine primary ECs have a limited growth potential, and the easy availability of murine ECs will facilitate the study of cavernous endothelial dysfunction in rats. This study was performed to establish immortalized rat penile cavernous ECs (rEC) and investigate how they could repair erectile dysfunction in rats with cavernous nerve injury (CNI). rEC was isolated enzymatically by collagenase digestion and were cultured. An amphotropic replication-incompetent retroviral vector encoding <i>v-myc</i> oncogene was used to transfect rEC for immortalization (vREC). Morphological and immunohistochemical properties of vREC were examined. Eight-week-old male Sprague-Dawley rats were divided into three groups of five rats each, including group 1 = sham operation, group 2 = bilateral CN injury, group 3 = vREC (1 × 10<sup>6</sup> cells) treatment after CNI. Erectile response was assessed at 2, 4 weeks after transplantation of vREC., Penile tissue were harvested at 4 weeks after transplantation and immune–histochemical examination was performed. vREC showed the expression of CD31, vWF, cell type-specific markers for EC by RT-PCR and flowcytometry. At 2, 4 weeks after transplantation, rats with CNI had significantly lower erectile function than control group (<i>p</i> < 0.05). The group transplanted with vREC showed higher erectile function than the group without vRECs (<i>p</i> < 0.05). vREC was established and repaired erectile dysfunction in rats with CNI. This cell line may be useful for studying mechanisms and drug screening of erectile dysfunction of rats.https://www.mdpi.com/1424-8247/16/1/123erectile dysfunctionendothelial cells<i>v-myc</i>
spellingShingle Sang Hong Bak
Jae Heon Kim
Seung U. Kim
Dong-Seok Lee
Yun Seob Song
Hong J. Lee
Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve Injury
Pharmaceuticals
erectile dysfunction
endothelial cells
<i>v-myc</i>
title Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve Injury
title_full Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve Injury
title_fullStr Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve Injury
title_full_unstemmed Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve Injury
title_short Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve Injury
title_sort established immortalized cavernous endothelial cells improve erectile dysfunction in rats with cavernous nerve injury
topic erectile dysfunction
endothelial cells
<i>v-myc</i>
url https://www.mdpi.com/1424-8247/16/1/123
work_keys_str_mv AT sanghongbak establishedimmortalizedcavernousendothelialcellsimproveerectiledysfunctioninratswithcavernousnerveinjury
AT jaeheonkim establishedimmortalizedcavernousendothelialcellsimproveerectiledysfunctioninratswithcavernousnerveinjury
AT seungukim establishedimmortalizedcavernousendothelialcellsimproveerectiledysfunctioninratswithcavernousnerveinjury
AT dongseoklee establishedimmortalizedcavernousendothelialcellsimproveerectiledysfunctioninratswithcavernousnerveinjury
AT yunseobsong establishedimmortalizedcavernousendothelialcellsimproveerectiledysfunctioninratswithcavernousnerveinjury
AT hongjlee establishedimmortalizedcavernousendothelialcellsimproveerectiledysfunctioninratswithcavernousnerveinjury