PMID- 24251583 OWN - NLM STAT- MEDLINE DCOM- 20140918 LR - 20190318 IS - 1743-6109 (Electronic) IS - 1743-6095 (Linking) VI - 11 IP - 2 DP - 2014 Feb TI - Intracavernous delivery of clonal mesenchymal stem cells restores erectile function in a mouse model of cavernous nerve injury. PG - 411-23 LID - 10.1111/jsm.12380 [doi] AB - INTRODUCTION: Recently, much attention has focused on stem cell therapy; bone marrow-derived stem cells (BMSCs) are one of the most studied mesenchymal stem cells used in the field of erectile dysfunction (ED). However, a major limitation for the clinical application of stem cell therapy is the heterogeneous nature of the isolated cells, which may cause different treatment outcomes. AIM: We investigated the effectiveness of mouse clonal BMSCs obtained from a single colony by using subfractionation culturing method (SCM) for erectile function in a mouse model of cavernous nerve injury (CNI). METHODS: Twelve-week-old C57BL/6J mice were divided into four groups: sham operation group, bilateral CNI group receiving a single intracavernous (IC) injection of phosphate-buffered saline (20 muL) or clonal BMSCs (3 x 10(5) cells/20 muL), and receiving a single intraperitoneal (IP) injection of clonal BMSCs (3 x 10(5) cells/20 muL). MAIN OUTCOME MEASURES: The clonal BMSC line was analyzed for cell-surface epitopes by using fluorescence-activated cell sorting and for differentiation potential. Two weeks after CNI and treatment, erectile function was measured by electrically stimulating the cavernous nerve. The penis was harvested for histologic examinations and Western blot analysis. RESULTS: Clonal BMSCs expressed cell surface markers for mesenchymal stem cells and were capable of differentiating into several lineages, including adipogenic, osteogenic, and chondrogenic cells. Both IC and IP injections of clonal BMSCs significantly restored cavernous endothelial and smooth muscle content, and penile nNOS and neurofilament content in CNI mice. IC injection of clonal BMSCs induced significant recovery of erectile function, which reached 90-100% of the sham control values, whereas IP injection of clonal BMSCs partially restored erectile function. CONCLUSION: We established a homogeneous population of mouse clonal BMSCs using SCM; clonal BMSCs successfully restored erectile function in CNI mice. The homogeneous nature of clonal mesenchymal stem cells may allow their clinical applications. CI - (c) 2013 International Society for Sexual Medicine. FAU - Ryu, Ji-Kan AU - Ryu JK AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. FAU - Kim, Da-Ham AU - Kim DH FAU - Song, Kang Moon AU - Song KM FAU - Yi, Tacghee AU - Yi T FAU - Suh, Jun-Kyu AU - Suh JK FAU - Song, Sun U AU - Song SU LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131120 PL - Netherlands TA - J Sex Med JT - The journal of sexual medicine JID - 101230693 RN - EC 1.14.13.39 (Nitric Oxide Synthase Type I) RN - EC 1.14.13.39 (Nos1 protein, mouse) SB - IM MH - Animals MH - Cell Differentiation MH - Cell Separation MH - Disease Models, Animal MH - Erectile Dysfunction/*etiology/*surgery MH - Injections MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*physiology MH - Mice MH - Mice, Inbred C57BL MH - Muscle, Smooth/physiology MH - Nitric Oxide Synthase Type I/metabolism MH - Penile Erection/*physiology MH - Penis/enzymology/*innervation/surgery MH - Peripheral Nerve Injuries/*complications MH - Regeneration OTO - NOTNLM OT - Cavernous Nerve Injury OT - Clonal Mesenchymal Stem Cell OT - Erectile Dysfunction OT - Mouse Model of Erectile Dysfunction OT - Stem Cell Therapy EDAT- 2013/11/21 06:00 MHDA- 2014/09/19 06:00 CRDT- 2013/11/21 06:00 PHST- 2013/11/21 06:00 [entrez] PHST- 2013/11/21 06:00 [pubmed] PHST- 2014/09/19 06:00 [medline] AID - S1743-6095(15)30658-5 [pii] AID - 10.1111/jsm.12380 [doi] PST - ppublish SO - J Sex Med. 2014 Feb;11(2):411-23. doi: 10.1111/jsm.12380. Epub 2013 Nov 20.