J Sex Med. 2010 Apr;7(4 Pt 1):1391-400. Epub 2010 Feb 5.
The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemiaassociated erectile dysfunction in a rat model.
Huang YC, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM, Lue TF, Lin CS.
Source
Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San
Francisco, CA, USA.
Abstract
INTRODUCTION:
Hyperlipidemia has been associated with erectile dysfunction (ED) via damage to the cavernous
endothelium and nerves. Adipose tissue-derived stem cells (ADSC) have been shown to
differentiate into endothelial cells and secrete vasculotrophic and neurotrophic factors.
AIM:
To assess whether ADSC have therapeutic effects on hyperlipidemia-associated ED.
METHODS:
Twenty-eight male rats were induced to develop hyperlipidemia with a high-fat diet
(hyperlipidemic rats, HR). Ten additional male rats were fed a normal diet to serve as controls
(normal rats, NR). Five months later, all rats were subjected to ADSC isolation from paragonadal
fat. The cells were cultured for 1 week, labeled with 5-ethynyl-2′-deoxyuridine (EdU), and then
injected autologously into the corpus cavernosum of 18 HR. The remaining 10 HR rats were
injected with phosphate buffered saline (PBS). At 2 and 14 days post-transplantation, four rats in
the HR + ADSC group were sacrificed for tracking of the transplanted cells. At 28 days posttransplantation,
all remaining rats were analyzed for serum biochemistry, erectile function, and
penile histology.
MAIN OUTCOME MEASURES:
Erectile function was assessed by intracavernous pressure (ICP) measurement during
electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and smooth muscle
were assessed by immunohistochemistry.
RESULTS:
Serum total cholesterol and low-density lipoprotein levels were significantly higher in HR than in
NR. High-density lipoprotein level was significantly lower in HR than in NR. Mean ICP/mean
arterial pressure ratio was significantly lower in HR + PBS than in NR + PBS or HR + ADSC.
Neuronal nitric oxide synthase (nNOS)-positive nerve fibers and endothelial cells were fewer in HR
+ PBS than in HR + ADSC. Smooth muscle content was significantly higher in both HR groups
than in NR.
CONCLUSIONS:
Hyperlipidemia is associated with abnormalities in both the nerves and endothelium. Treatment
with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for ED.
Int J Impot Res. 2011 Nov-Dec;23(6):268-75. doi: 10.1038/ijir.2011.38. Epub 2011 Jul 28.
Tracking intracavernously injected adipose-derived stem cells to bone marrow.
Lin G, Qiu X, Fandel T, Banie L, Wang G, Lue TF, Lin CS.
Source
Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA 94143-0738, USA.
Abstract
The intracavernous (i.c.) injection of stem cells (SCs) has been shown to improve erectile function in various erectile dysfunction (ED) animal models. However, the tissue distribution of the injected cells remains unknown. In this study we tracked i.c.-injected adipose-derived stem cells (ADSCs) in various tissues. Rat paratesticular fat was processed for ADSC isolation and culture. The animals were then subject to cavernous nerve (CN) crush injury or sham operation, followed by i.c. injection of 1 million autologous or allogeneic ADSCs that were labeled with 5-ethynyl-2-deoxyuridine (EdU). Another group of rats received i.c. injection of EdU-labeled allogeneic penile smooth muscle cells (PSMCs). At 2 and 7 days post injection, penises and femoral bone marrow were processed for histological analyses. Whole femoral bone marrows were also analyzed for EdU-positive cells by flow cytometry. The results show that ADSCs exited the penis within days of i.c. injection and migrated preferentially to bone marrow. Allogenicity did not affect the bone marrow appearance of ADSCs at either 2 or 7 days, whereas CN injury reduced the number of ADSCs in bone marrow significantly at 7 but not 2 days. The significance of these results in relation to SC therapy for ED is discussed.
PMID:21796145[PubMed – indexed for MEDLINE]PMCID:PMC3516363