Abstract
Background and Objectives: Stem cell therapy is a novel treatment with regenerative ability that can treat erectile dysfunction (ED). This phase 1/2 clinical trial (NCT02945449) using 2 consecutive intracavernous (IC) injections of allogeneic Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) was studied for the first time in the treatment of diabetic patients with ED. The primary outcome was to assess the safety and tolerability, and the secondary outcome was to assess the efficacy of 2 consecutive IC injections of allogeneic WJ-MSCs in diabetic ED. Patients and Methods: Twenty-two diabetic patients with refractory ED were included. Two consecutive IC injections of allogeneic WJ-MSCs were performed. Tolerability was assessed immediately, and at 24 h, safety was evaluated for 12 months. Efficacy was assessed using International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS), and Color Duplex Doppler Ultrasound for 12 months. Results: The procedure was well-tolerated. Minimal and transient adverse events were redness and bruising at the site of injections. There were no patient-reported serious adverse effects. There were significant improvements in IIEF-5, EHS, peak systolic velocity (PSV) basal, and 20-min PSV, all over the follow-up time points in comparison to the baseline. Conclusion: This is the first human study with proven tolerability, safety, and efficacy of IC injections of allogeneic WJ-MSCs for the treatment of diabetic patients with ED.
Journal Section:
Editor's choice
References
1.
Korneyev
IA
, Alexeeva
TA
, Al-Shukri
SH
, Bernikov
AN
, Erkovich
AA
, Kamalov
AA
, . Prevalence and risk factors for erectile dysfunction and lower urinary tract symptoms in Russian Federation men: analysis from a national population-based multicenter study
. Int J Impot Res
. 2016 Mar–Apr
;28
(2
):74
–9
.2.
Gerber
RE
, Vita
JA
, Ganz
P
, Wager
CG
, Araujo
AB
, Rosen
RC
, . Association of peripheral microvascular dysfunction and erectile dysfunction
. J Urol
. 2015
;193
(2
):612
–7
.3.
Divers
J
, Mayer-Davis
EJ
, Lawrence
JM
, Isom
S
, Dabelea
D
, Dolan
L
, . Trends in incidence of type 1 and type 2 diabetes among youths: selected counties and Indian reservations, United States, 2002–2015
. MMWR Morb Mortal Wkly Rep
. 2020
;69
(6
):161
–5
.4.
Corona
G
, Giorda
CB
, Cucinotta
D
, Guida
P
, Nada
E
, Aglialoro
A
, . Sexual dysfunction in type 2 diabetes at diagnosis: progression over time and drug and non-drug correlated factors
. PLoS One
. 2016
;11
(10
):e0157915
.5.
Mazzilli
R
, Elia
J
, Delfino
M
, Benedetti
F
, Scordovillo
G
, Mazzilli
F
. Prevalence of diabetes mellitus (DM) in a population of men affected by Erectile Dysfunction (ED)
. Clin Ter
. 2015
;166
(5
):e317
.6.
Porst
H
, Burnett
A
, Brock
G
, Ghanem
H
, Giuliano
F
, Glina
S
, . SOP conservative (medical and mechanical) treatment of erectile dysfunction
. J Sex Med
. 2013
;10
(1
):130
–71
.7.
Alwaal
A
, Zaid
UB
, Lin
CS
, Lue
TF
. Stem cell treatment of erectile dysfunction
. Adv Drug Deliv Rev
. 2015
;82-83
:137
–44
.8.
Dashwood M
R
, Crump
A
, Shi-Wen
X
, Loesch
A
. Identification of neuronal nitric oxide synthase (nNOS) in human penis: a potential role of reduced neuronally-derived nitric oxide in erectile dysfunction
. Curr Pharm Biotechnol
. 2011
;12
(9
):1316
–21
.9.
Zhou
F
, Xin
H
, Liu
T
, Li
GY
, Gao
ZZ
, Liu
J
, . Effects of icariside II on improving erectile function in rats with streptozotocin-induced diabetes
. J Androl
. 2012 Sep–Oct
;33
(5
):832
–44
.10.
Stuckey
BGA
, Jadzinsky
MN
, Murphy
LJ
, Montorsi
F
, Kadioglu
A
, Fraige
F
, . Sildenafil citrate for treatment of erectile dysfunction in men with type 1 diabetes: Results of a randomized controlled trial
. Diabetes Care
. 2003
;26
(2
):279
–84
.11.
Wang
X
, Liu
C
, Xu
Y
, Chen
P
, Shen
Y
, Xu
Y
, . Combination of mesenchymal stem cell injection with icariin for the treatment of diabetes-associated erectile dysfunction
. PLoS One
. 2017
;12
(3
):1
–18
.12.
Gokce
A
, Peak
TC
, Abdel-Mageed
AB
, Hellstrom
WJ
. Adipose tissue-derived stem cells for the treatment of erectile dysfunction
. Curr Urol Rep
. 2016
;17
(2
):1
–7
.13.
Ryu
JK
, Kim
DH
, Song
KM
, Ryu
DS
, Kim
SN
, Shin
DH
, . Intracavernous delivery of clonal mesenchymal stem cells rescues erectile function in the streptozotocin-induced diabetic mouse
. Andrology
. 2016
;4
(1
):172
–84
.14.
Albersen
M
, Kendirci
M
, van der Aa
F
, Hellstrom
WJ
, Lue
TF
, Spees
JL
. Multipotent stromal cell therapy for cavernous nerve injury-induced erectile dysfunction
. J Sex Med
. 2012
;9
(2
):385
–403
.15.
Wang
HS
, Hung
SC
, Peng
ST
, Huang
CC
, Wei
HM
, Guo
YJ
, . Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord
. Stem Cells
. 2004
;22
(7
):1330
–7
.16.
Karahuseyinoglu
S
, Cinar
O
, Kilic
E
, Kara
F
, Akay
GG
, Demiralp
DO
, . Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys
. Stem Cells
. 2007 Feb
;25
(2
):319
–31
.17.
Fong
CY
, Richards
M
, Manasi
N
, Biswas
A
, Bongso
A
. Comparative growth behaviour and characterization of stem cells from human Wharton’s jelly
. Reprod Biomed Online
. 2007
;15
(6
):708
–18
.18.
Pittenger
MF
, Mackay
AM
, Beck
SC
, Jaiswal
RK
, Douglas
R
, Mosca
JD
, . Multilineage potential of adult human mesenchymal stem cells
. Science
. 1999
;284
(5411
):143
–7
.19.
Abediankenari
S
, Ghasemi
M
. Generation of immune inhibitory dendritic cells and CD4+T regulatory cells inducing by TGF-β
. Iran J Allergy Asthma Immunol
. 2009
;8
(1
):25
–30
.20.
Haahr
MK
, Jensen
CH
, Toyserkani
NM
, Andersen
DC
, Damkier
P
, Sørensen
JA
, . Safety and potential effect of a single intracavernous injection of autologous adipose-derived regenerative cells in patients with erectile dysfunction following radical prostatectomy: an open-label phase I clinical trial
. EBioMedicine
. 2016
;5
:204
–10
.21.
Levy
JA
, Marchand
M
, Iorio
L
, Cassini
W
, Zahalsky
MP
. Determining the feasibility of managing erectile dysfunction in humans with placental-derived stem cells
. J Am Osteopath Assoc
. 2016
;116
(1
):e1
–5
.22.
Sarugaser
R
, Lickorish
D
, Baksh
D
, Hosseini
MM
, Davies
JE
. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors
. Stem Cells
. 2005
;23
(2
):220
–9
.23.
Margossian
T
, Reppel
L
, Makdissy
N
, Stoltz
JF
, Bensoussan
D
, Huselstein
C
. Mesenchymal stem cells derived from Wharton’s jelly: comparative phenotype analysis between tissue and in vitro expansion
. Biomed Mater Eng
. 2012
;22
(4
):243
–54
.24.
Al Demour
S
, Jafar
H
, Adwan
S
, Alsharif
A
, Alhawari
H
, Alrabadi
A
, . Safety and potential therapeutic effect of two intracavernous autologous bone marrow derived mesenchymal stem cells injections in diabetic patients with erectile dysfunction: an open label phase I clinical trial
. Urol Int
. 2018
;101
(3
):358
.25.
Bieri
M
, Said
E
, Antonini
G
, Dickerson
D
, Tuma
J
, Bartlett
CE
, . Phase I and registry study of autologous bone marrow concentrate evaluated in PDE5 inhibitor refractory erectile dysfunction
. J Transl Med
. 2020
;18
(1
):24
–7
.26.
Yiou
R
, Hamidou
L
, Birebent
B
, Bitari
D
, Le Corvoisier
P
, Contremoulins
I
, . Intracavernous injections of bone marrow mononucleated cells for postradical prostatectomy erectile dysfunction: final results of the INSTIN clinical trial
. Eur Urol Focus
. 2017
;3
(6
):643
–5
.27.
Haahr
MK
, Harken Jensen
C
, Toyserkani
NM
, Andersen
DC
, Damkier
P
, Sørensen
JA
, . A 12-month follow-up after a single intracavernous injection of autologous adipose-derived regenerative cells in patients with erectile dysfunction following radical prostatectomy: an open-label phase I clinical trial
. Urology
. 2018
;121
:203.e6
–13
.28.
Bahk
JY
, Jung
JH
, Han
H
, Min
SK
, Lee
YS
. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases
. Exp Clin Transplant
. 2010
;8
(2
):150
.29.
Leungwattanakij
S
, Bivalacqua
TJ
, Usta
MF
, Yang
DY
, Hyun
JS
, Champion
HC
, . Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum
. J Androl
. 2003 Mar–Apr
;24
(2
):239
–45
.30.
Ning
H
, Qiu
X
, Baine
L
, Lin
G
, Lue
TF
, Lin
CS
. Effects of high glucose on human cavernous endothelial cells
. Urology
. 2012
;80
(5
):1162
–11
.© 2021 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2021
You do not currently have access to this content.
