Abstract

Objective: The primary objective of this core is to produce and provide monoclonal antibodies (Mab's) specific for unique surface markers that characterize specific stages during stem-cell to beta-cell maturation. By combining forefront expertise in relevant promoter selection with different stem-cell sources to produce staged cells that are expandable we will apply state-of-the-art hybridoma technology/phage-display library large scale screening to produce and identify such antibodies. In addition, micro-array-analysis of such cells may allow identification of potential cell surface antigens for Mab or polyclonal antibody generation. Antibodies directed against unique surface markers will be mandatory future tools to monitor ex vivo stem-cell maturation towards the mature beta-cell. Such antibodies will allow not only selection of desired sub- populations (FACS/MACS)-but moreover facilitate screening assays for factors necessary to drive the maturation process in descrete steps. Such progress is mandatory for reaching the long term goal of being able to produce fully normal non-modified beta-cells from desired stem-cell sources. Additionally, Mab's or polyclonal antisera against stage-specific internal markers, including transcription factors will be produced to facilitate documentation of the success of the maturation process.

  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 #
1U19DK061244-01
Application #
6452416
Study Section
Special Emphasis Panel (ZDK1)
Project Start
2001-09-01
Project End
2006-08-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Hale, Michael A; Swift, Galvin H; Hoang, Chinh Q et al. (2014) The nuclear hormone receptor family member NR5A2 controls aspects of multipotent progenitor cell formation and acinar differentiation during pancreatic organogenesis. Development 141:3123-33
Kumar, Anujith; Lo Nigro, Antonio; Gysemans, Conny et al. (2013) Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells. PLoS One 8:e63491
Beucher, Anthony; Martin, Merce; Spenle, Caroline et al. (2012) Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development. Dev Biol 361:277-85
Pauwelyn, Karen; Roelandt, Philip; Notelaers, Tineke et al. (2011) Culture of mouse embryonic stem cells with serum but without exogenous growth factors is sufficient to generate functional hepatocyte-like cells. PLoS One 6:e23096
Roelandt, Philip; Pauwelyn, Karen Ann; Sancho-Bru, Pau et al. (2010) Human embryonic and rat adult stem cells with primitive endoderm-like phenotype can be fated to definitive endoderm, and finally hepatocyte-like cells. PLoS One 5:e12101
Galbo, T; Pedersen, I L; Floyel, T et al. (2010) Novel monoclonal antibodies against Pdx1 reveal feedback regulation of Pdx1 protein levels. Eur J Histochem 54:e19
Soyer, Josselin; Flasse, Lydie; Raffelsberger, Wolfgang et al. (2010) Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell development. Development 137:203-12
Roelandt, Philip; Sancho-Bru, Pau; Pauwelyn, Karen et al. (2010) Differentiation of rat multipotent adult progenitor cells to functional hepatocyte-like cells by mimicking embryonic liver development. Nat Protoc 5:1324-36
Hald, Jacob; Sprinkel, Anne Ejrnaes; Ray, Michael et al. (2008) Generation and characterization of Ptf1a antiserum and localization of Ptf1a in relation to Nkx6.1 and Pdx1 during the earliest stages of mouse pancreas development. J Histochem Cytochem 56:587-95
Sahin, M Behnan; Schwartz, Robert E; Buckley, Shannon M et al. (2008) Isolation and characterization of a novel population of progenitor cells from unmanipulated rat liver. Liver Transpl 14:333-45

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