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iPS Therapy of ERectile Dysfunction in a Rat Model of Type 2 Diabetes and Obesity
Summary Data Summary
Applicant Gonzalez-Cadavid, Nestor
E-Mail Address ncadavid@ucla.edu
Project Title iPS Therapy of ERectile Dysfunction in a Rat Model of Type 2 Diabetes and
Obesity
CBU ID 14GHSU1398
External SubContract ID 25732-47
Diabetic Complication Uropathy
Funding Program Group Pilot & Feasibility [PF2014]
Abstract 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
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 37549
Supply Total Costs 6500
Equipment Total Costs 0
Travel/Other Total Costs 9248
Direct Costs 53297
Indirect Costs Proposed 16735
Total Costs Proposed 70032
Total Costs Approved 70031
Start Date 10/1/2014
End Date 9/30/2015
IFO Name Hansberry, Jim
IFO E-Mail Address jhansberry@labiomed.org
IACUC/IRB No. 999999
IACUC/IRB Institution Harbor-UCLA Medical Center
Entity ID No. 1952138184A1
Report Request Date 10/30/2015
T1D NO
TypeCount
Invoices 8
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  14GHSU139825732-47Harbor-UCLA Medical Center9/28/2015$5,838.96-$5,838.96-View PDF
  View  14GHSU139825732-47Harbor-UCLA Medical Center8/17/2015$8,677.67-$8,677.67-View PDF
  View  14GHSU139825732-47Harbor-UCLA Medical Center7/27/2015$9,925.56-$9,925.56-View PDF
  View  14GHSU139825732-47Harbor-UCLA Medical Center6/17/2015$11,111.00-$11,111.00-View PDF
  View  14GHSU139825732-47Harbor-UCLA Medical Center5/21/2015$23,014.25-$23,014.25-View PDF
  View  14GHSU139825732-47Harbor-UCLA Medical Center4/20/2015$6,670.83-$6,670.83-View PDF
  View  14GHSU139825732-47Harbor-UCLA Medical Center3/20/2015$705.78-$705.78-View PDF
  View  14GHSU139825732-47Harbor-UCLA Medical Center10/16/2015$4,086.95-$4,086.95-View PDF
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