Document Detail


Transdifferentiation of rat fetal brain stem cells into penile smooth muscle cells.
MedLine Citation:
PMID:  19220248     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: To evaluate whether rat fetal brain stem cells can be induced to acquire cell fates outside the nervous system, hypothesising that cell-based replacement therapy with stem cells can aid in the regeneration of penile smooth musculature and might help to attenuate organic erectile dysfunction (ED), as the degeneration of penile smooth muscle cells leading to subsequent impairment of function is important in organic ED. MATERIALS AND METHODS: Fetal brain stem cells (FBSCs) from embryonal 12-day Fisher 344 rats were isolated and characterized. For in vitro studies, undifferentiated FBSCs were cultured for 21 days in either N2 media (control) or N2 media conditioned in rat penile smooth muscle cell culture. These were then subjected to immunocytochemistry for specific markers of neural stem cells (nestin) and penile smooth muscle cells, i.e. alpha-smooth muscle actin (alphaSMA), penis-specific myosin light chain (MLC) desmin, calponin, vimentin, phosphodiesterase-5 (PDE5) and connexin. For in vivo studies, male adult Fisher 344 rats had an intracavernous injection with saline (five rats, control) or FBSCs that were labelled genetically by an expression construct for green fluorescent protein (GFP, nine rats, experimental) and maintained for 6 weeks. The rats were then killed and penile tissue was harvested and subjected to immunocytochemistry for markers of neural stem cells, smooth muscle cells, and sinusoidal endothelium (vascular endothelial growth factor, VEGF). RESULTS: Undifferentiated cells exposed to N2 media continued to maintain the characteristic morphological and protein marker features of FBSCs, while the cells exposed to the conditioned media acquired the morphological features of smooth muscle cells. In addition, the differentiated cells (30-40%) expressed smooth muscle markers. Rats implanted with FBSCs had cells that showed double-labelling for GFP/alphaSMA, GFP/calponin and GFP/VEGF. The control group had no evidence of such double-labelling. CONCLUSIONS: These results suggest the transdifferentiation of FBSCs into penile smooth muscle cells. Such transdifferentiated cells showed long-term survival when injected into the cavernous tissue, thus raising the possibility of a novel therapeutic option for organic ED.
Authors:
Yunseob Song; Neal Mehta; Bryant Sheh; Farid Saljooque; Hoi Sang U; Mahadevan Rajasekaran
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-11
Journal Detail:
Title:  BJU international     Volume:  104     ISSN:  1464-410X     ISO Abbreviation:  BJU Int.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-14     Completed Date:  2009-08-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100886721     Medline TA:  BJU Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  257-62     Citation Subset:  IM    
Affiliation:
Department of Urology, Soonchunhyang University College of Medicine, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / cytology
Cell Transdifferentiation / physiology*
Erectile Dysfunction / therapy*
Fetal Stem Cells / cytology*
Immunohistochemistry
Male
Myocytes, Smooth Muscle / cytology*
Penis / cytology*
Rats
Rats, Inbred F344
Vascular Endothelial Growth Factor A / metabolism
Chemical
Reg. No./Substance:
0/Vascular Endothelial Growth Factor A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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