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Modeling the Renal Interstitium for Nephron Regeneration
Summary Data Summary
Applicant Humphreys, Benjamin
E-Mail Address bhumphre@dom.wustl.edu
Project Title Modeling the Renal Interstitium for Nephron Regeneration
CBU ID 14GHSU1406
External SubContract ID 25732-58
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2014]
Abstract The revolution in pluripotent stem cell biology, and subsequent insight
regarding the differentiation of these cells into discrete tissues, has shown
that self-organization during development is a biologic principle across organs.
In vitro, embryonic stem cells can be coaxed to differentiate into nephron-like
structures in a petri-dish - pointing towards a new strategy for generating
fully differentiated nephrons ex vivo. Progress to date in generating
self-organizing nephron-like structures in vitro has been limited to the
epithelial compartment, including tubules and glomeruli-like structures.
Ultimately, functioning nephrons will require a surrounding interstitial
component, including stromal cells such as pericytes and fibroblasts, as well as
pertubular capillaries. But there has been no study of regneration or modeling
this compartment in vitro to date. This pilot application will address this
knowledge gap with the goal of generating a renal interstitial environment in
vitro. Our unique advance is that we have identified a previously unrecognized
kidney resident cell type defined by expression of the transcription factor Gli1
which marks resident kidney mesenchymal stem cells (MSC). These cells are CD31-,
F4/80-, CD45-, PDGFRß+, Sca1+, CD29+, CD105+, representing a consensus MSC
surface profile. Moreover, they possess trilineage differentiation capacity and
tightly associate with vascular endothelial cells both in vivo and in vitro.
Our central hypothesis is that Gli1+ mesenchymal stem cells from kidney serve as
an interstitial stem cell population. We further hypothesize that these cells
will function to organize and regenerate the interstitial compartment by
stabilizing endothelial tubes, giving rise to supportive pericytes and
fibroblasts and interacting with epithelial basement membrane. We have designed
a series of experiments to assess the ability of these stem cells to
recapitulate and model the kidney interstitium in vitro, a critical step toward
regenerating functional nephrons in vitro.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 28997
Supply Total Costs 3516
Equipment Total Costs 0
Travel/Other Total Costs 2097
Direct Costs 34610
Indirect Costs Proposed 25390
Total Costs Proposed 60000
Total Costs Approved 60000
Start Date 10/1/2014
End Date 9/30/2015
IFO Name Destouche, Anastasie
IFO E-Mail Address adestouche1@partners.org
IACUC/IRB No. 04474
IACUC/IRB Institution Brigham and Womens Hospital
Entity ID No.
Report Request Date 10/30/2015
T1D NO
TypeCount
Invoices 5
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  14GHSU140625732-58Brigham and Womens Hospital6/16/2015$18,233.14-$18,233.14-View PDF
  View  14GHSU140625732-58Brigham and Womens Hospital5/11/2015$21,305.39-$21,305.39-View PDF
  View  14GHSU140625732-58Brigham and Womens Hospital4/9/2015$8,498.95-$8,498.95-View PDF
  View  14GHSU140625732-58Brigham and Womens Hospital3/10/2015$6,515.60-$6,515.60-View PDF
  View  14GHSU140625732-58Brigham and Womens Hospital2/10/2015$5,446.92-$5,446.92-View PDF
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