This article has been retracted at the authors' request.

BACKGROUND AND OBJECTIVES: Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. METHODS AND RESULTS: Oral ulcers were induced by topical application of formocresol in the oral cavity of dogs. Transplantation of undifferentiated GFP-labeled Autologous Bone Marrow Stem Cell (BMSCs), Adipose Derived Stem Cell (ADSCs) or vehicle (saline) was injected around the ulcer in each group. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) was detected in MSCs by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Expression of VEGF and collagen genes was detected in biopsies from all ulcers. Results: MSCs expressed mRNA for VEGF MSCs transplantation significantly accelerated oral ulcer healing compared with controls. There was increased expression of both collagen and VEGF genes in MSCs-treated ulcers compared to controls. CONCLUSIONS: MSCs transplantation may help to accelerate oral ulcer healing, possibly through the induction of angiogenesis by VEGF together with increased intracellular matrix formation as detected by increased collagen gene expression. This body of work has provided evidence supporting clinical applications of adipose-derived cells in safety and efficacy trials as an alternative for bone marrow mesenchymal stem cells in oral ulcer healing.
Adipose Tissue ; Adult Stem Cells ; Animals ; Biopsy ; Bone Marrow ; Collagen ; Dogs ; Formocresols ; Gene Expression ; Mesenchymal Stromal Cells ; Mouth ; Oral Ulcer ; Regenerative Medicine ; RNA, Messenger ; Stem Cells ; Tissue Engineering ; Transplants ; Ulcer ; Vascular Endothelial Growth Factor A

AIMTo assess heme oxygenase-1 (HO-1) activity in the cavernous tissue of sildenafil citrate-treated rats.

METHODSOne hundred and ninety-two Sprague-Dawley male rats, divided into four equal groups, were investigated. Group 1, the control group, received regular animal chow; group 2 received sildenafil citrate by intragastric tube; group 3 received sildenafil and HO inhibitor (zinc protoporphyrin, ZnPP); and group 4 received sildenafil and nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester (L-NAME). Twelve rats from each group were killed after 0.5 h, 1 h, 2 h and 3 h of drug administration. Then HO-1 activity, cGMP levels and NOS enzymatic activity in the cavernous tissues were estimated.

RESULTSIn cavernous tissue, HO-1 activity, NOS enzymatic activity and cGMP concentration increased significantly in sildenafil-treated rats compared to other groups throughout the experiment. Rats receiving either HO or NOS inhibitors showed a significant decrease in these parameters. HO-1 cavernous tissue activity and NOS enzymatic activity demonstrated a positive significant correlation with cGMP levels (r = 0.646, r = 0.612 respectively; P < 0.001).

CONCLUSIONThe actions of PDE5 inhibitor sildenafil citrate in the cavernous tissue are partly mediated through the interdependent relationship between both HO-1 and NOS activities.

Administration, Oral ; Animals ; Cyclic GMP ; metabolism ; Drug Interactions ; Drug Therapy, Combination ; Enzyme Inhibitors ; pharmacology ; Heme Oxygenase-1 ; antagonists & inhibitors ; metabolism ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide Synthase ; metabolism ; Penis ; drug effects ; enzymology ; Piperazines ; pharmacology ; Protoporphyrins ; pharmacology ; Purines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate ; Sulfones ; pharmacology ; Vasodilator Agents ; pharmacology