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

• Published in: International journal of molecular sciences 2018-11, Vol.19 (12), p.3730
• Main Authors: Jeon, Seung Hwan, Zhu, Guan Qun, Bae, Woong Jin, Choi, Sae Woong, Jeong, Hyun Cheol, Cho, Hyuk Jin, Ha, U-Syn, Hong, Sung-Hoo, Lee, Ji Youl, Kwon, Eun Bi, Kim, Hyo-Jin, Lee, Soon Min, Kim, Hey-Yon, Kim, Sae Woong
• Format: Article
• Language: English
• Subjects: AKT protein; Angiogenesis; Apoptosis; BAX protein; Bcl-2 protein; Beta cells; Bone marrow; Caspase-3; Cell adhesion & migration; Diabetes; Diabetes mellitus; Erectile dysfunction; Fibroblast growth factor 2; Growth factors; intracavernosal injection; Mesenchymal stem cells; Muscles; Nitric oxide; Nitric-oxide synthase; Proteins; Quantitative analysis; SDF-1 protein; Smooth muscle; Stem cell transplantation; Stem cells; Streptozocin; streptozotocin-induced diabetic rats; stromal cell-derived factor-1 expressing engineered mesenchymal stem cells; Vascular endothelial growth factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19123730

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 ( = 48) were divided into four groups ( = 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 ( < 0.05). SDF-1 eMSC treatment improved the smooth muscle content in the corpus cavernosum ( < 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 ( < 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 ( < 0.05). Higher levels of phosphorylated protein kinase B (p-AKT)/protein kinase B (AKT) ( < 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 ( < 0.05). SDF-1 eMSCs showed beneficial effects on recovery from erectile function.