Correction of Diabetic Erectile Dysfunction with Adipose Derived Stem Cells Modified with the Vascular Endothelial Growth Factor Gene in a Rodent Diabetic Model

Abstract

The aim of this study was to determine whether adipose derived stem cells (ADSCs) expressing vascular endothelial growth factor (VEGF) gene can improve endothelial function, recover the impaired VEGF signaling pathway and enhance smooth muscle contents in a rat diabetic erectile dysfunction (DED) model. DED rats were induced via intraperitoneal injection of streptozotocin (40 mg/kg), and then screened by apomorphine (100 µg/kg). Five groups were used (n = 12/group)–Group 1 (G1): intracavernous injection of lentivirus-VEGF; G2: ADSCs injection; G3: VEGF-expressing ADSCs injection; G4: Phosphate buffered saline injection; G1–G4 were DED rats; G5: normal rats. The mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured at days 7 and 28 after the injections. The components of the VEGF system, endothelial, smooth muscle, pericytes markers in cavernoursal tissue were assessed. On day 28 after injection, the group with intracavernosum injection of ADSCs expressing VEGF displayed more efficiently and significantly raised ICP and ICP/MAP (p<0.01) than those with ADSCs or lentivirus-VEGF injection. Western blot and immunofluorescent analysis demonstrated that improved erectile function by ADSCs-VEGF was associated with increased expression of endothelial markers (VEGF, VEGF R1, VEGF R2, eNOS, CD31 and vWF), smooth muscle markers (a-actin and smoothelin), and pericyte markers (CD146 and NG2). ADSCs expressing VEGF produced a therapeutic effect and restored erectile function in diabetic rats by enhancing VEGF-stimulated endothelial function and increasing the contents of smooth muscle and pericytes.

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

“…The enhanced proliferation and anti-oxidant capacity may contribute to the retention of stem cells. However, the amount of EPCs-hTERT retained in corpus cavernous was still too small to explain the therapeutic effect, which was similar to previous studies [18,32] and indicates that other mechanisms may exist.…”

“…Stem cells transplanted into rat corpus cavernous have the potential to differentiate toward endothelial cells or smooth cells [31]. However, very few stem cells were successfully tracked after intracavernous application in a series of studies for ED treatments using stem cells [18,32]. Oxidative stress and other irregular microenvironments may contribute to the loss of transplanted stem cells.…”

“…Previous studies successfully applied genetically modified stem cells for ED treatment [13,18,19]. However, whether hTERT overexpression enhanced EPCs-based treatment of DMED was not demonstrated.…”

137 Superparamagnetic Iron Oxide Nanoparticle Targeting of Adipose Tissue-Derived Stem Cells in Diabetes-Associated Erectile Dysfunction

“…7,25 All animals were anesthetized with isoflurane, and a 1.5-cm oblique incision was made to expose the penis. The corpus cavernosum was then gently cannulated using a 28-gauge needle, and each rat received an injection of either 0.5 ml PBS (Cont.…”

“…6 Stem cells restore impaired endothelial cell and cavernous smooth muscle cell functions in DED by secreting multiple growth factors, preventing programmed endothelial cell death, and differentiating into smooth muscle and endothelial cells. [7][8][9][10][11] Intracavernous (IC) injection of cultured adipose tissue-derived stem cells (ADSCs) has improved erectile function and increased the contents of smooth muscle and endothelial cells in a rat model of DED. 12 However, the main route of stem cell delivery, i.e., IC injection, transfers cells directly into the target site, and thus very few labeled ADSCs are found in the corpus cavernosum, which limits the therapeutic potential.…”