Correction of diabetic erectile dysfunction with adipose derived stem cells modified with the vascular endothelial growth factor gene in a rodent diabetic model

PLoS One. 2013 Aug 30;8(8):e72790. doi: 10.1371/journal.pone.0072790. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Biomarkers / metabolism
  • Blood Glucose / metabolism
  • Body Weight
  • Cells, Cultured
  • Diabetes Complications / blood
  • Diabetes Complications / physiopathology
  • Diabetes Complications / therapy*
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Erectile Dysfunction / blood
  • Erectile Dysfunction / complications
  • Erectile Dysfunction / physiopathology
  • Erectile Dysfunction / therapy*
  • Genetic Therapy*
  • Humans
  • Male
  • Myocytes, Smooth Muscle / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Pericytes / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Streptozocin
  • Transfection
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / therapeutic use*

Substances

  • Biomarkers
  • Blood Glucose
  • Vascular Endothelial Growth Factor A
  • Streptozocin
  • Nitric Oxide Synthase Type III
  • Receptors, Vascular Endothelial Growth Factor

Grants and funding

This work was funded by the grant from the National Natural Science Foundation of China (30872571,81070488, 30901487 and 81270696)(http://www.nsfc.gov.cn/Portal0/default152.htm), the grant of Research Fund for the Doctoral Program of Higher Education of China (20100171110060)(http://www.cutech.edu.cn/cn/kyjj/gdxxbsdkyjj/A010301index_1.htm), the Guangdong Natural Science Fund (S2011010005282, 10251008901000005)(http://gdsf.gdstc.gov.cn/);and the Guangdong Province Science & Technology Project(2011B031800115, 2011B032000003, 20101051500032)(http://pro.gdstc.gov.cn/stms/main.jsp). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.