Human Urine-Derived Stem Cells Alone or Genetically-Modified with FGF2 Improve Type 2 Diabetic Erectile Dysfunction in a Rat Model

Abstract

AimThe aim of this study was to determine the possibility of improving erectile dysfunction using cell therapy with either human urine-derived stem cells (USCs) or USCs genetically-modified with FGF2 in a type 2 diabetic rat model.MethodsHuman USCs were collected from 3 healthy donors. USCs were transfected with FGF2 (USCs-FGF2). Sixty-five SD male rats were divided into five groups (G). A control group of normal rats (G1, n = 10), and four other test groups of type 2 diabetic erectile dysfunction rats: PBS as a negative control (G2, n = 10), USCs (G3, n = 15), lentivirus-FGF2 (G4, n = 15), and USCs-FGF2 (G5, n = 15). Diabetes was induced in the rats via a high fat diet for 28 days and a subsequent intraperitoneal injection of streptozotocin (35 mg/kg). Erectile dysfunction was screened with apomorphine (100 μg/kg). Cell injections in the test groups (G2–G5) occurred directly into the corpora cavernosa. The implanted cells were tracked at 7 days (n = 5 animals/G) and 28 days (n = 10 animals/G) post injection. Mean arterial pressure (MAP), intracavernosal pressure (ICP), expression of endothelial markers (CD31, VEGF and eNOS), smooth muscle markers (desmin and smoothelin), histological changes and erectile function were assessed for each group.ResultsUSCs expressed mesenchymal stem cell markers, and secreted a number of proangiogenic growth factors. USCs expressed endothelial cell markers (CD31 and vWF) after transfection with FGF2. Implanted USCs or USCs-FGF2 displayed a significantly raised ICP and ICP/MAP ratio (p<0.01) 28 days after intracavernous injection. Although few cell were detected within the implanted sites, histological and western blot analysis demonstrated an increased expression of endothelial and smooth muscle markers within the cavernous tissue following USC or USC-FGF2 injection.ConclusionsThe paracrine effect of USCs or USCs-FGF2 induced improvement of erectile function in type 2 diabetic rats by recruiting resident cells and increasing the endothelial expression and contents of smooth muscle.

Recent Progress in Stem Cell Therapy for Diabetic Nephropathy

“…For treatment of DN, the application of USCs is still at its infancy. Ouyang et al [46] reported that human USCs genetically modified with fibroblast growth factor 2 (FGF2) relieved type 2 diabetic symptoms in a rat model. However, the role of USCs in the diabetic kidney remains unclear.…”

Extracellular Vesicles Secreted by Human Urine-Derived Stem Cells Promote Ischemia Repair in a Mouse Model of Hind-Limb Ischemia

“…In addition, another team of researchers reported that USCs have the capability to differentiate into endothelial, urothelial and smooth muscle cells [14,15]. In previous urological studies, USCs were used to construct tissue-engineered conduits for urinary diversion [15] and to ameliorate erectile dysfunction [16,17]. Moreover, we found that USCs combined with bioactive materials accelerated skin-wound healing in rabbits [18] and that USCs can survive in and migrate to other parenchymal areas and differentiate into neuron-like cells in the rat brain [13].…”

890 Treatment of diabetes mellitus-induced erectile dysfunction using endothelial progenitor cells genetically modified with human telomerase reverse transcriptase

“…The secretion of trophic growth factors emerged as the main mechanism to explain the therapeutic effect of stem cells in the treatment of ED [33,34]. Various studies demonstrated that stem cells secrete many growth factors, including CXCL5, adrenomedullin, bFGF, VEGF, nerve growth factor and BDNF [19,[34][35][36].…”

“…Various studies demonstrated that stem cells secrete many growth factors, including CXCL5, adrenomedullin, bFGF, VEGF, nerve growth factor and BDNF [19,[34][35][36]. These growth factors exhibit potent angiogenic and neurotrophic activities.…”