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. MATERIALS AND METHODS MDSCs were obtained from mouse muscle, and shown by immunocytochemistry for α-smooth muscle actin (αSMA) 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), αSMA, and smoothelin, and also by Western blot for αSMA and PCNA. MDSC differentiation was confirmed by the activation of the αSMA promoter-linked β-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.