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Int J Mol Sci. 2018 Nov 23;19(12). pii: E3730. doi: 10.3390/ijms19123730.

Engineered Mesenchymal Stem Cells Expressing Stromal Cell-derived Factor-1 Improve Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats.

Jeon SH1,2,3, Zhu GQ4,5, Bae WJ6,7, Choi SW8, Jeong HC9,10, Cho HJ11, Ha US12, Hong SH13, Lee JY14, Kwon EB15,16, Kim HJ17, Lee SM18, Kim HY19, Kim SW20,21,22.

Author information

1
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. shwan52@naver.com.
2
Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Seoul 06591, Korea. shwan52@naver.com.
3
Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul 06591, Korea. shwan52@naver.com.
4
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. xiaoguanqun1@gmail.com.
5
Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Seoul 06591, Korea. xiaoguanqun1@gmail.com.
6
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. bwoong@catholic.ac.kr.
7
Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Seoul 06591, Korea. bwoong@catholic.ac.kr.
8
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. lifeisa9ame@catholic.ac.kr.
9
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. koulich@naver.com.
10
Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Seoul 06591, Korea. koulich@naver.com.
11
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. hyukjincho0403@gmail.com.
12
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. ushamd@catholic.ac.kr.
13
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. toomey@catholic.ac.kr.
14
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. uroljy@catholic.ac.kr.
15
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. eunbi9859@naver.com.
16
Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Seoul 06591, Korea. eunbi9859@naver.com.
17
Department of Stem cell therapy, SL BIGEN, Seongnam 13488, Korea. hjkim@slbigen.com.
18
Department of Stem cell therapy, SL BIGEN, Seongnam 13488, Korea. smlee@slbigen.com.
19
Department of Stem cell therapy, SL BIGEN, Seongnam 13488, Korea. hykim@slbigen.com.
20
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. ksw1227@catholic.ac.kr.
21
Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Seoul 06591, Korea. ksw1227@catholic.ac.kr.
22
Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul 06591, Korea. ksw1227@catholic.ac.kr.

Abstract

Effective therapies for erectile dysfunction (ED) associated with diabetes mellitus (DM) are needed. In this study, the effects of stromal cell-derived factor-1 (SDF-1)-expressing engineered mesenchymal stem cells (SDF-1 eMSCs) and the relevant mechanisms in the corpus cavernosum of a streptozotocin (STZ)-induced DM ED rat model were evaluated. In a randomized controlled trial, Sprague⁻Dawley (SD) rats (n = 48) were divided into four groups (n = 12/group): Normal (control), DM ED (diabetes induced by STZ), DM ED + BM-MSC (treated with bone marrow [BM]-derived MSCs), and DM ED + SDF-1 eMSC (treated with SDF-1-expressing BM-MSCs). After four weeks, intracavernosal pressure (ICP), an indicator of erectile function, was 0.75 ± 0.07 in the normal group, 0.27 ± 0.08 in the DM ED group, 0.42 ± 0.11 in the DM ED + BM-MSC group, and 0.58 ± 0.11 in the DM ED + SDF-1 eMSC group. BM-MSCs, especially SDF-1 eMSCs, improved ED (p < 0.05). SDF-1 eMSC treatment improved the smooth muscle content in the corpus cavernosum (p < 0.05). As SDF-1 expression increased, ED recovery improved. In the SDF-1 eMSC group, levels of neuronal nitric oxide synthase (nNOS) and phosphorylated endothelial NOS (p-eNOS) were higher than those in other groups (p < 0.05). In addition, high stromal cell-derived factor-1 (SDF-1) expression was associated with increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in DM ED rats (p < 0.05). Higher levels of phosphorylated protein kinase B (p-AKT)/protein kinase B (AKT) (p < 0.05) and B-cell lymphoma-2 (Bcl-2) and lower levels of the apoptosis factors Bcl2-associated x (Bax) and caspase-3 were observed in the MSC-treated group than in the DM ED group (p < 0.05). SDF-1 eMSCs showed beneficial effects on recovery from erectile function.

KEYWORDS:

erectile dysfunction; intracavernosal injection; streptozotocin-induced diabetic rats; stromal cell-derived factor-1 expressing engineered mesenchymal stem cells

PMID:
30477146
PMCID:
PMC6321323
DOI:
10.3390/ijms19123730
[Indexed for MEDLINE]
Free PMC Article

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