Abstract

The main goal of Project #2 is to determine how precursor/stem cells develop in an in vivo transplantation environment. The tools for characterizing the cell populations before and after transplantation are laser capture microdissection (LSM). Expression arrays and morphology. The project also provides an opportunity to use gene expression arrays to better characterize human islet preparations in hopes of finding ways to better predict clinical outcome.
Aim 1. Evaluation of human islet preparations for gene expression using LCM and gene arrays. Studies will be performed on in situ islets in the pancreas, on """"""""healthy"""""""" isolated islets preparations and on less healthy islets. The work could lead to a practical simple test to determine the transplant potential of isolated human islets.
Aim 2. Determination of the fate of human islets after transplantation. The major goal is to see in human precursor/stems contained in human islet preparations can form new beta cells in a graft site. The acute loss of beta-cells after transplantation will be determined and the remodeling of these grafts over time will be assessed.
Aim 3. Differentiation of Transplanted Stem Cells (NIPs, ductal progenitors, SP cells, and others). It will be determine dif in vivo transplant sites provide a beneficial environment for the further development of precursor/stem cells that have been preconditioned in vitro.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19DK061251-01
Application #
6452427
Study Section
Special Emphasis Panel (ZDK1)
Project Start
2001-09-30
Project End
2006-09-29
Budget Start
Budget End
Support Year
1
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
Joslin Diabetes Center
Department
Type
DUNS #
071723084
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Goldfine, Allison B; Patti, Mary Elizabeth (2015) New lessons from gastric bypass: Impact of glucose-independent islet function. Obesity (Silver Spring) 23:1942-3
Shen, Keyue; Luk, Samantha; Hicks, Daniel F et al. (2014) Resolving cancer-stroma interfacial signalling and interventions with micropatterned tumour-stromal assays. Nat Commun 5:5662
Jermendy, A; Toschi, E; Aye, T et al. (2011) Rat neonatal beta cells lack the specialised metabolic phenotype of mature beta cells. Diabetologia 54:594-604
Aye, Tandy; Toschi, Elena; Sharma, Arun et al. (2010) Identification of markers for newly formed beta-cells in the perinatal period: a time of recognized beta-cell immaturity. J Histochem Cytochem 58:369-76
Hamamoto, Yoshiyuki; Akashi, Tomoyuki; Inada, Akari et al. (2010) Lack of evidence for recipient precursor cells replenishing ?-cells in transplanted islets. Cell Transplant 19:1563-72
Dodge, Rikke; Loomans, Cindy; Sharma, Arun et al. (2009) Developmental pathways during in vitro progression of human islet neogenesis. Differentiation 77:135-47
Yano, Tatsuya; Liu, Zhengyu; Donovan, Jennifer et al. (2007) Stromal cell derived factor-1 (SDF-1)/CXCL12 attenuates diabetes in mice and promotes pancreatic beta-cell survival by activation of the prosurvival kinase Akt. Diabetes 56:2946-57
Rukstalis, J Michael; Habener, Joel F (2007) Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas. Gene Expr Patterns 7:471-9
Rukstalis, J Michael; Ubeda, Mariano; Johnson, Megan V et al. (2006) Transcription factor snail modulates hormone expression in established endocrine pancreatic cell lines. Endocrinology 147:2997-3006
Noguchi, Hirofumi; Matsushita, Masayuki; Matsumoto, Shinichi et al. (2005) Mechanism of PDX-1 protein transduction. Biochem Biophys Res Commun 332:68-74

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