Nestor Gonzalez-Cadavid

Personal Information
Title Professor
Expertise Uropathy
Institution Harbor-UCLA Medical Center
Data Summary
TypeCount
Grants/SubContracts 1
Progress Reports 1
Publications 1
Protocols 0
Committees 2
Experiments 0
Strains 0
Models 0

SubContract(s)


iPS Therapy of ERectile Dysfunction in a Rat Model of Type 2 Diabetes and Obesity
Abstract. Erectile dysfunction (ED) is prevalent in type 2 diabetes mellitus (T2DM), mainly in obese patients, frequently does not respond to glycemic control alone or palliative PDE5 inhibitors, impairs the quality of life, and is a burden on public health costs. T2DM-ED is mostly due to the impairment of the smooth muscle (SM) compliance in the penile corpora cavernosa, causing corporal veno-occlusive dysfunction (CVOD), resembling what occurs in the media SM of the arterial tree in arteriosclerosis/ hypertension, thus being a sentinel of vascular disease. Stem cell therapy for T2DM-related ED is promising, but there are hurdles that induced pluripotent stem cells (iPS) may overcome. This may be tested in the only T2DM rat model with conclusively described CVOD, the obese Zucker (OZ) rats. The aim is to determine whether: a) intracorporal implant of OZ rats with iPS ameliorates ED and the underlying corporal histopathology induced by T2DM and obesity; b) concurrent glycemic control in the host may reduce the noxious effects of T2DM on the iPS once implanted; c) tissue repair by iPS occurs in part by their cross-talk with endogenous penile stem cells (PSC), leading to a differentiation of both types of stem cells and/or paracrine modulation of differentiated cells, that may be impaired by hyperglycemia/dyslipidemia. Exp. 1 will study the effect of iPs from mouse fibroblasts on the penile corporal histopathology and CVOD induced by T2DM in OZ rats, in the presence of diabetes control, through in vivo cross-talk with PSC. OZ rats (5.5 months old) will be implanted into the penile corpora cavernosa with mouse fibroblasts iPS generated with a construct of Oct4, Sox2, Klf4, and myc, or with vehicle only. A third group will receive the iPS with concurrent pioglitazone in the chow for glycemic control. The effects on CVOD and the underlying corporal histopathology, and the potential mediation of PSC, will be defined at 45 days. Exp. 2 will study in vitro the relative contributions of direct differentiation, paracrine stimulation and stem cell cross-talk on the iPS modulation of corporal cell replenishment, and whether this may be affected by hyperglycemia and dyslipidemia. Mouse iPS and OZ rat PSC will be tested either individually for 1 and 7 days or in dual cultures where the iPS cross-talk with the PSC, under the influence of high glucose or dyslipidemia will be followed. Relevance: Erectile dysfunction (ED) in type 2 diabetes (T2DM) and obesity has a considerable biomedical significance. This project will be conducted on a validated rat model of T2DM-ED and aims to: a) define a novel stem cell therapy approach based on the implant into the penis of induced pluripotent stem cells (iPS), generated from easily obtainable differentiated cells, to prevent or regress the pathophysiology that causes ED; and b) clarify the interaction of these iPS with the endogenous penile stem cells and how this is affected by T2DM


Progress Reports

Annual Reports

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