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JDRF Funded Research

JDRF-Funded Research: Progress Report

Name: Susan Bonner-Weir ,Ph.D.
Joslin Diabetes Center, USA
Lab Website:

Project duration: 01-FEB-2004 to 31-JAN-2007
Priority Research Grant

Project grant award: $495,000.00*

* Total Grant award amount may vary depending on budget adjustments and it is contingent upon research progress and availability of JDRF research funds.

File No: 1-2004-120

(Abstract Dt: 15-AUG-2003)

Therapeutic Area: Beta Cell Therapies

Grant Status: Inactive

Project Title

Phenotypic analysis of new beta cells

Accomplishments

1. The expression pattern of ten of these candidate markers have been characterized by immunostaining and/or PCR analysis in the Px model. We found differential expression for D6.1a, Surfactant D, glypican 3, CD24, MMP2, CD39L1 and CK19 whereas the ribosomal S25 was unchanged. 2. We assessed whether these markers were universal for indicating new b cells we turned to neonatal rat islets of less than 24, 24 and 24-48 hours of age. The expression of several of the top candidate genes, including CD24 antigen (CD24), keratin 19 (CK19), surfactant D and matrix metalloproteinase-2 (MMP-2) was confirmed by immunohistochemistry in neonatal islets. Furthermore, these markers of new b cells were transiently expressed. 3. We modified the islet isolation procedure in order to obtain neonatal islets within the first days after birth. PCR analysis confirmed the expression of CK19, MMP2, D6.1a, Frizzled, D6.1a, CD24, and Gly-3 mRNAs in adult ducts and neonatal islets but not in adult islets.

Publications/Presentations

1.Toschi E, Aye T, Fuller A, Gaudet J, Sharma A, Weir G, Sgroi D, Bonner-Weir S. Gene expression profiling of new b cells: evidence for differentiating b cells passing through a ductal phenotype. Diabetes. 2004. 53, suppl. 2: Abstract 2. Aye A, Toschi E, Gaudet J, Fuller A, Sharma A, Bonner-Weir S. Transient expression of duct genes in new and neonatal b cells: evidence for ductal origin? Poster presentation Beta Cell Biology consortium Retreat. 2004 3. Aye T, Toschi E, Gaudet J, Sharma A, Sgroi D, Bonner-Weir S. Ductal origin of b cells suggested by transient expression of markers in new b cells in rats. Oral presentation at Lawson-Wilkins Pediatric Society meeting 2004. 4. Bonner-Weir S, Toschi E, Inada A, Reitz P, Fonseca SY, Aye T, Sharma A. The pancreatic ductal epithelium serves as a potential pool of progenitor cells. Pediatric Diabetes 2004 (in press) 5. Bonner-Weir S, Toschi E, Inada A, Aye T, Sharma A. Generation of islets from pancreatic progenitor cells. In: Stem Cell and Gene-Based Therapy: Frontiers in Regenerative Medicine" , Battler A and Leor J,eds. 2004 (in press).

Who benefits from the research

One important outcome of this research will be the development of markers for the earliest b cells, a tool that should lead to future identification of the precursor/stem cells that give rise to b cells after birth. Being able to identify and characterize new b cells should lead to a better understanding of the life history of the pancreatic b cell and the stage of differentiation of newly derived insulin producing cells from stem/progenitor cells. Thus the scientific community working on generating more b cells will benefit and eventually patients with diabetes. Future Plans: We have about 5 markers that we are starting to apply these markers to different stages and models in order to address the questions in Specific aim 2. We will continue testing other markers as in Specific Aim 1 by immunostaining and RT-PCR so that we may have markers with overlapping time of expression. We will start to test the markers for cell sorting first with the neonatal tissue; we will generate new antibodies if needed