title: Effect of muscle-derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat.
abstract: OBJECTIVE
  To determine whether skeletal muscle-derived stem cells (MDSCs) convert into smooth muscle cells (SMCs) both in vitro and in vivo, and in so doing ameliorate the erectile dysfunction (ED) of aged rats, and whether endogenous stem cells are present in the rat corpora cavernosa.
  
  
  METHODS
  MDSCs were obtained from mouse muscle, and shown by immunocytochemistry for alpha-smooth muscle actin (alpha SMA) to originate in vitro in myofibroblasts and SMCs, discriminating SMCs by calponin 1 expression. In vivo these MDSCs, labelled with 4',6-diamidino-2-phenylindole, were implanted into the corpora cavernosa of young adult (5-month old) and aged (20-month old) rats for 2 and 4 weeks. Histological changes were assessed by immunohistochemistry and quantitative Western blot. Functional changes were determined by electrical field stimulation (EFS) of the cavernosal nerve.
  
  
  RESULTS
  The exogenous cells replicated and converted into SMCs, as shown in corporal tissue sections by confocal immunofluorescence microscopy for proliferating cell nuclear antigen (PCNA), alpha SMA, and smoothelin, and also by Western blot for alpha SMA and PCNA. MDSC differentiation was confirmed by the activation of the alpha SMA promoter-linked beta-galactosidase in transfected cells, both in vitro and after implantation in the corpora. Putative endogenous stem cells were shown in corporal tissue sections and Western blots by detecting CD34 and a possible Sca1 variant. EFS showed that implanted MDSCs raised in aged rats the maximal intracavernosal pressure/mean arterial pressure levels above (2 weeks) or up to (4 weeks) those of young adult rats.
  
  
  CONCLUSIONS
  MDSCs implanted into the corpora cavernosa of aged rats converted into SMCs and corrected ED, and endogenous cells expressing stem cell markers were also found in untreated tissue. This suggests that exogenous stem cell implantation and/or endogenous stem cell modulation might be viable therapeutic approaches for ageing-related ED.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Urology Research Laboratory, Torrance, CA 90509, USA.
authors.forename: Gaby
authors.initials: G
authors.lastname: Nolazco
authors.forename: Istvan
authors.initials: I
authors.lastname: Kovanecz
authors.forename: Dolores
authors.initials: D
authors.lastname: Vernet
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gelfand
authors.forename: James
authors.initials: J
authors.lastname: Tsao
authors.forename: Monica G
authors.initials: MG
authors.lastname: Ferrini
authors.forename: Thomas
authors.initials: T
authors.lastname: Magee
authors.forename: Jacob
authors.initials: J
authors.lastname: Rajfer
authors.forename: Nestor F
authors.initials: NF
authors.lastname: Gonzalez-Cadavid
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D007150:Immunohistochemistry; D018783:Impotence, Vasculogenic / Q000473:pathology / Q000628:therapy*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000637:transplantation*; D010413:Penis / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*