PMID- 26711324 OWN - NLM STAT- MEDLINE DCOM- 20161230 LR - 20181202 IS - 2047-2927 (Electronic) IS - 2047-2919 (Linking) VI - 4 IP - 1 DP - 2016 Jan TI - Intracavernous delivery of clonal mesenchymal stem cells rescues erectile function in the streptozotocin-induced diabetic mouse. PG - 172-84 LID - 10.1111/andr.12138 [doi] AB - 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 muL) or clonal BMSCs (3 x 10(5) cells/20 muL). 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 alpha-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. CI - (c) 2015 American Society of Andrology and European Academy of Andrology. FAU - Ryu, J-K AU - Ryu JK AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. AD - Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, Korea. FAU - Kim, D-H AU - Kim DH AD - Translational Research Center, Inha University School of Medicine, Incheon, Korea. FAU - Song, K-M AU - Song KM AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. FAU - Ryu, D-S AU - Ryu DS AD - Department of Urology, Sungkyunkwan University School of Medicine, Samsung Changwon Hospital, Changwon, Korea. FAU - Kim, S-N AU - Kim SN AD - Drug Development Program, Department of Medicine, Inha University School of Medicine, Incheon, Korea. FAU - Shin, D-H AU - Shin DH AD - SCM Lifescience Co., Ltd., Incheon, Korea. FAU - Yi, T AU - Yi T AD - Translational Research Center, Inha University School of Medicine, Incheon, Korea. FAU - Suh, J-K AU - Suh JK AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. FAU - Song, S U AU - Song SU AD - Translational Research Center, Inha University School of Medicine, Incheon, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151229 PL - England TA - Andrology JT - Andrology JID - 101585129 RN - 0 (Actins) RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 0 (alpha-smooth muscle actin, mouse) RN - 5W494URQ81 (Streptozocin) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type I) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 1.14.13.39 (Nos3 protein, mouse) SB - IM MH - Actins/analysis MH - Animals MH - Cell- and Tissue-Based Therapy/*methods MH - Diabetes Complications/*therapy MH - Diabetes Mellitus, Experimental/metabolism MH - Disease Models, Animal MH - Erectile Dysfunction/*therapy MH - Intermediate Filaments/metabolism MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology MH - Mice, Inbred C3H MH - Mice, Inbred C57BL MH - Nitric Oxide Synthase Type I/analysis MH - Nitric Oxide Synthase Type III/analysis MH - Penile Erection/*physiology MH - Phosphorylation MH - Platelet Endothelial Cell Adhesion Molecule-1/analysis MH - Recovery of Function MH - Streptozocin OTO - NOTNLM OT - angiogenesis OT - clonal mesenchymal stem cell OT - diabetes OT - penile erection OT - stem cell therapy EDAT- 2015/12/30 06:00 MHDA- 2016/12/31 06:00 CRDT- 2015/12/30 06:00 PHST- 2015/04/02 00:00 [received] PHST- 2015/09/02 00:00 [revised] PHST- 2015/10/26 00:00 [accepted] PHST- 2015/12/30 06:00 [entrez] PHST- 2015/12/30 06:00 [pubmed] PHST- 2016/12/31 06:00 [medline] AID - 10.1111/andr.12138 [doi] PST - ppublish SO - Andrology. 2016 Jan;4(1):172-84. doi: 10.1111/andr.12138. Epub 2015 Dec 29.