Induction of Pancreatic Phenotypes in Central Nervous System Derived Pluripotential Progenitor Cells

F. Saljooque; A. Ho; B. Wu; A. Zahra; H. S. U

doi:10.1055/s-0030-1255105

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2011; 119(2): 101-110
DOI: 10.1055/s-0030-1255105

Article

Induction of Pancreatic Phenotypes in Central Nervous System Derived Pluripotential Progenitor Cells

F. Saljooque¹ , A. Ho¹ , B. Wu¹ , A. Zahra¹ , H. S. U¹

¹Division of Neurological Surgery, Veterans Administration San Diego Health Care System and The University of California – San Diego, San Diego, California, USA

Abstract

Fetal rat brain stem cells (RSCs) have been induced to express pituitary properties when exposed to pituitary cells ([U et al., 2002]). In this study, we explored whether these RSCs could also be influenced to acquire properties characteristic of the pancreas. To this end, RSCs in culture were exposed to media conditioned by rat islet tumor cells and media containing Exendin-4 and nicotinamide since both have been shown to induce pancreatic phenotypes in embryonic stem cells. Lastly, an expression construct for pdx-1 was introduced into RSCs. The expression of pancreatic markers was analyzed using RT-PRC and immunocytochemistry. When RSCs were exposed to rat islet tumor cell conditioned media and media containing Exendin-4 and nicotinamide, the expression of pdx-1, insulin and somatostatin were observed. They also acquired a spherical shape typical of pancreatic cells in culture. Under these varied conditions, transcriptional factors essential to pancreatic development such as pdx-1 and Isl-1 were induced. The critical role of pdx-1 in stimulating certain endocrine pancreatic properties in RSCs was further confirmed upon the introduction of an expression construct for pdx-1 which markedly induced insulin and somatostatin. Taken together, these findings suggests that fetal brain stem cells are pluripotent and can be reprogrammed to acquire pancreatic properties through pathways which involved the transcription factor Pdx1.

Key words

diabetes - pituitary adenoma - receptors

Full Text

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Correspondence

H. S. U MD

Division of Neurosurgery

The Veteran's Administration

Healthcare System

3350 La Jolla Village

Dr. La Jolla

CA 92037

USA

Phone: +1/858/552 8585 ext. 3093

Fax: +1/858/552 4376

Email: hoisang@ucsd.edu