Harnessing the regenerative effects of human amniotic stem cells (hAFSCs) on restoring erectile function in a bilateral cavernous nerve crush (BCNC) injury rat model

Abstract Background Intracavernous (IC) injections of stem cells has been shown to ameliorate cavernous nerve (CN)-induced erectile dysfunction (ED). However, the regenerative effects underlying the recovery of erectile function (EF) in human amniotic fluid-derived stem cells (hAFSCs) remain unclear...

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Main Authors: Chun-Hou Liao, Xiao-Wen Tseng, Chellappan Praveen Rajneesh, Yu-Jen Chang, Ming-Song Tsai, Wen-Chun Hsu, Kuo-Chiang Chen, Yi-No Wu
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-024-03972-1
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author Chun-Hou Liao
Xiao-Wen Tseng
Chellappan Praveen Rajneesh
Yu-Jen Chang
Ming-Song Tsai
Wen-Chun Hsu
Kuo-Chiang Chen
Yi-No Wu
author_facet Chun-Hou Liao
Xiao-Wen Tseng
Chellappan Praveen Rajneesh
Yu-Jen Chang
Ming-Song Tsai
Wen-Chun Hsu
Kuo-Chiang Chen
Yi-No Wu
author_sort Chun-Hou Liao
collection DOAJ
description Abstract Background Intracavernous (IC) injections of stem cells has been shown to ameliorate cavernous nerve (CN)-induced erectile dysfunction (ED). However, the regenerative effects underlying the recovery of erectile function (EF) in human amniotic fluid-derived stem cells (hAFSCs) remain unclear. In the bilateral cavernous nerve crushing (BCNC) injury rat paradigm, we sought to ascertain the effects of hAFSC treatment on EF recovery during the incipient phase. Methods Three groups of 45 male rats were used in this study: sham (Group 1), saline IC injection after BCNC (Group 2), and hAFSC intracavernous injection (ICI) after BCNC (Group 3). hAFSCs from the fourth passage showed potential to differentiate into trilineage cells. All animals were subjected to EF analysis on the 28th day post-injection and tissues were retrieved for histopathological and immunohistochemical analyses. Results IC injections of hAFSC significantly improved EF parameters in BCNC-ED rats at 28 days post-injury. AFSC treatment enhanced the smooth muscle condition and increased the smooth muscle/collagen ratio, as evidenced by histological analysis. Immunohistology revealed increased expression of 𝛼-SMA andvWf in the corpus cavernosum and enhanced expression of nNOS in the dorsal penile nerve in BCNC-ED rats (p < 0.05). Western blotting showed that hAFSC treatment significantly increased α-SMA expression in the hAFSC group compared with that in the BCNC group. Electron microscopy revealed significantly elevated myelination in the CN (p < 0.05), maintenance of smooth muscle structures, and restoration of EF in BCNC-ED rats treated with hAFSC. Discussion and conclusions hAFSC treatment increased EF in BCNC-ED rats at a single dose. As BCNC-ED resembles ED caused by radical prostatectomy (RP), this therapy has high potential for ED patients after RP surgery. Graphical Abstract
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spelling doaj-art-f005deb4391b4b5ea8d75b5b70c685f52024-11-10T12:11:01ZengBMCStem Cell Research & Therapy1757-65122024-11-0115111610.1186/s13287-024-03972-1Harnessing the regenerative effects of human amniotic stem cells (hAFSCs) on restoring erectile function in a bilateral cavernous nerve crush (BCNC) injury rat modelChun-Hou Liao0Xiao-Wen Tseng1Chellappan Praveen Rajneesh2Yu-Jen Chang3Ming-Song Tsai4Wen-Chun Hsu5Kuo-Chiang Chen6Yi-No Wu7Division of Urology, Department of Surgery, Cardinal Tien HospitalProgram in Pharmaceutical Biotechnology, College of Medicine, Fu Jen Catholic UniversitySchool of Medicine, College of Medicine, Fu Jen Catholic UniversityBioresource Collection and Research Center, Food Industry Research and Development InstituteSchool of Medicine, College of Medicine, Fu Jen Catholic UniversityGraduate Institute of Nutrition and Food Sciences, Fu Jen Catholic UniversitySchool of Medicine, College of Medicine, Fu Jen Catholic UniversitySchool of Medicine, College of Medicine, Fu Jen Catholic UniversityAbstract Background Intracavernous (IC) injections of stem cells has been shown to ameliorate cavernous nerve (CN)-induced erectile dysfunction (ED). However, the regenerative effects underlying the recovery of erectile function (EF) in human amniotic fluid-derived stem cells (hAFSCs) remain unclear. In the bilateral cavernous nerve crushing (BCNC) injury rat paradigm, we sought to ascertain the effects of hAFSC treatment on EF recovery during the incipient phase. Methods Three groups of 45 male rats were used in this study: sham (Group 1), saline IC injection after BCNC (Group 2), and hAFSC intracavernous injection (ICI) after BCNC (Group 3). hAFSCs from the fourth passage showed potential to differentiate into trilineage cells. All animals were subjected to EF analysis on the 28th day post-injection and tissues were retrieved for histopathological and immunohistochemical analyses. Results IC injections of hAFSC significantly improved EF parameters in BCNC-ED rats at 28 days post-injury. AFSC treatment enhanced the smooth muscle condition and increased the smooth muscle/collagen ratio, as evidenced by histological analysis. Immunohistology revealed increased expression of 𝛼-SMA andvWf in the corpus cavernosum and enhanced expression of nNOS in the dorsal penile nerve in BCNC-ED rats (p < 0.05). Western blotting showed that hAFSC treatment significantly increased α-SMA expression in the hAFSC group compared with that in the BCNC group. Electron microscopy revealed significantly elevated myelination in the CN (p < 0.05), maintenance of smooth muscle structures, and restoration of EF in BCNC-ED rats treated with hAFSC. Discussion and conclusions hAFSC treatment increased EF in BCNC-ED rats at a single dose. As BCNC-ED resembles ED caused by radical prostatectomy (RP), this therapy has high potential for ED patients after RP surgery. Graphical Abstracthttps://doi.org/10.1186/s13287-024-03972-1Erectile dysfunctionBCNC injuryhAFSCStem cellsElectron microscopy
spellingShingle Chun-Hou Liao
Xiao-Wen Tseng
Chellappan Praveen Rajneesh
Yu-Jen Chang
Ming-Song Tsai
Wen-Chun Hsu
Kuo-Chiang Chen
Yi-No Wu
Harnessing the regenerative effects of human amniotic stem cells (hAFSCs) on restoring erectile function in a bilateral cavernous nerve crush (BCNC) injury rat model
Stem Cell Research & Therapy
Erectile dysfunction
BCNC injury
hAFSC
Stem cells
Electron microscopy
title Harnessing the regenerative effects of human amniotic stem cells (hAFSCs) on restoring erectile function in a bilateral cavernous nerve crush (BCNC) injury rat model
title_full Harnessing the regenerative effects of human amniotic stem cells (hAFSCs) on restoring erectile function in a bilateral cavernous nerve crush (BCNC) injury rat model
title_fullStr Harnessing the regenerative effects of human amniotic stem cells (hAFSCs) on restoring erectile function in a bilateral cavernous nerve crush (BCNC) injury rat model
title_full_unstemmed Harnessing the regenerative effects of human amniotic stem cells (hAFSCs) on restoring erectile function in a bilateral cavernous nerve crush (BCNC) injury rat model
title_short Harnessing the regenerative effects of human amniotic stem cells (hAFSCs) on restoring erectile function in a bilateral cavernous nerve crush (BCNC) injury rat model
title_sort harnessing the regenerative effects of human amniotic stem cells hafscs on restoring erectile function in a bilateral cavernous nerve crush bcnc injury rat model
topic Erectile dysfunction
BCNC injury
hAFSC
Stem cells
Electron microscopy
url https://doi.org/10.1186/s13287-024-03972-1
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