Bone marrow-derived mesenchymal stromal cell therapy in a rat model of cavernous nerve injury: Preclinical study for approval.
Although clinical studies using stem cells to treat erectile dysfunction have been performed or are ongoing, there is little consensus on the optimal protocol. We aimed to develop a protocol optimizing human bone marrow-derived mesenchymal stromal cell (hBMSC) therapy in a rat model of cavernous nerve injury.



We performed, in order, a dose-finding study, a toxicokinetic study of hBMSCs, and a study to determine the timing and number of cell injections.



From the dose-finding study, 1 × 10(6) cells were selected as the dose per hBMSC injection. From the toxicokinetic study, 14 days was selected as the interval between repeat treatments. In the final study, the ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the control group than in the sham group (23.4% vs. 55.1%, P <0.001). An immediate single injection of hBMSCs significantly improved erectile function compared with the control group (39.8%, P = 0.035), whereas a delayed single injection showed improvement with a marginal trend (38.1%, P = 0.079). All histomorphometric changes were significantly more improved in the immediate or delayed single injection groups than in the control group. Repeat treatments did not provide any benefit for the recovery of erectile function and histomorphometric changes.



Intracavernous injection of 1 × 10(6) hBMSCs results in a recovery of penile erection and histomorphometric changes in a rat model of cavernous nerve injury, even when treatment was delayed until 4 weeks after cavernous nerve injury.
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Dalsan
D
You
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Myoung Jin
MJ
Jang
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Bo Hyun
BH
Kim
Pharmicell Co. Ltd., Seongnam, Gyeonggi, Republic of Korea.
Ki Ryung
KR
Choi
Department of Urology, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Gyeongsangnam, Republic of Korea.
Chunwoo
C
Lee
Department of Urology, Kangwon National University Hospital, Chuncheon, Kangwon, Republic of Korea.
Geehyun
G
Song
Pharmicell Co. Ltd., Seongnam, Gyeonggi, Republic of Korea.
Ha Chul
HC
Shin
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
In Gab
IG
Jeong
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Nayoung
N
Suh
Pharmicell Co. Ltd., Seongnam, Gyeonggi, Republic of Korea.
Yong Man
YM
Kim
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Tai Young
TY
Ahn
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: cskim@amc.seoul.kr.
Choung-Soo
CS
Kim
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002470:Cell Survival; D004195:Disease Models, Animal; D017277:Drug Approval; D006801:Humans; D016130:Immunophenotyping; D007267:Injections; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010413:Penis / Q000293:injuries* / Q000294:innervation*; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
cavernous nerve; impotence; penile erection; prostatectomy; stem cell transplantation