title: Intracavernous delivery of clonal mesenchymal stem cells rescues erectile function in the streptozotocin-induced diabetic mouse.
abstract: The major hurdle for the clinical application of stem cell therapy is the heterogeneous nature of the isolated cells, which may cause different treatment outcomes. The aim of this study was to examine the effectiveness of mouse clonal bone marrow-derived stem cells (BMSCs) obtained from a single colony by using subfractionation culturing method for erectile function in diabetic animals. Twelve-week-old C57BL/6J mice were divided into four groups: controls, diabetic mice, and diabetic mice treated with a single intracavernous injection of PBS (20 μL) or clonal BMSCs (3 × 10(5) cells/20 μL). Clonal BMSCs were isolated from 5-week-old C3H mice. Two weeks after treatment, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was stained with antibodies to PECAM-1, smooth muscle α-actin, neuronal nitric oxide synthase (nNOS), neurofilament, and phosphorylated endothelial NOS (phospho-eNOS). We also performed Western blot for phospho-eNOS, and eNOS in the corpus cavernosum tissue. Local delivery of clonal BMSCs significantly restored cavernous endothelial and smooth muscle cell contents, and penile nNOS and neurofilament contents, and induced eNOS phosphorylation (Ser1177) in diabetic mice. Intracavernous injection of clonal BMSCs induced significant recovery of erectile function, which reached 80-90% of the control values. Clonal BMSCs successfully restored erectile function through dual angiogenic and neurotrophic effects in diabetic mice. The homogenous nature of clonal mesenchymal stem cells may allow their clinical applications and open a new avenue through which to treat diabetic erectile dysfunction.
authors.affiliation: National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.|Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, Korea.
authors.forename: J-K
authors.initials: JK
authors.lastname: Ryu
authors.affiliation: Translational Research Center, Inha University School of Medicine, Incheon, Korea.
authors.forename: D-H
authors.initials: DH
authors.lastname: Kim
authors.affiliation: National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
authors.forename: K-M
authors.initials: KM
authors.lastname: Song
authors.affiliation: Department of Urology, Sungkyunkwan University School of Medicine, Samsung Changwon Hospital, Changwon, Korea.
authors.forename: D-S
authors.initials: DS
authors.lastname: Ryu
authors.affiliation: Drug Development Program, Department of Medicine, Inha University School of Medicine, Incheon, Korea.
authors.forename: S-N
authors.initials: SN
authors.lastname: Kim
authors.affiliation: SCM Lifescience Co., Ltd., Incheon, Korea.
authors.forename: D-H
authors.initials: DH
authors.lastname: Shin
authors.affiliation: Translational Research Center, Inha University School of Medicine, Incheon, Korea.
authors.forename: T
authors.initials: T
authors.lastname: Yi
authors.affiliation: National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
authors.forename: J-K
authors.initials: JK
authors.lastname: Suh
authors.affiliation: Translational Research Center, Inha University School of Medicine, Incheon, Korea.
authors.forename: S U
authors.initials: SU
authors.lastname: Song
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D048909:Diabetes Complications / Q000628:therapy*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000628:therapy*; D007382:Intermediate Filaments / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D052248:Nitric Oxide Synthase Type I / Q000032:analysis; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D010410:Penile Erection / Q000502:physiology*; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D020127:Recovery of Function; D013311:Streptozocin
chemical_list: D000199:Actins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C544013:alpha-smooth muscle actin, mouse; D013311:Streptozocin; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: angiogenesis; clonal mesenchymal stem cell; diabetes; penile erection; stem cell therapy