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TISSUE-SPECIFIC STEM CELLS

Enrichment of Putative Pancreatic Progenitor Cells from Mice by Sorting for Prominin1 (CD133) and Platelet-Derived Growth Factor Receptor β

^aDepartment of Surgery and
^b21st Century Center of Excellence Program, Center of Excellence for Signal Transduction Disease: Diabetes Mellitus as Model, Kobe University Graduate School of Medicine, Kobe, Japan

Key Words. Pancreas • Tissue-specific stem cells • Diabetes • Insulin-producing cells • Prominin1 • CD133

Correspondence: Correspondence: Yuichi Hori, M.D., Ph.D., Department of Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Telephone: 81-78-382-6302; Fax: 81-78-382-6307; e-mail: horiy{at}med.kobe-u.ac.jp

Received on February 26, 2008; accepted for publication on August 5, 2008.

First published online in STEM CELLS EXPRESS  August 14, 2008.

Success in islet transplantation-based therapies for type 1 diabetes mellitus and an extreme shortage of pancreatic islets have motivated recent efforts to develop renewable sources of islet-replacement tissue. Although pancreatic progenitor cells hold a promising potential, only a few attempts have been made at the prospective isolation of pancreatic stem/progenitor cells, because of the lack of specific markers and the development of effective cell culture methods. We found that prominin1 (also known as CD133) recognized the undifferentiated epithelial cells, whereas platelet-derived growth factor receptor β (PDGFRβ) was expressed on the mesenchymal cells in the mouse embryonic pancreas. We then developed an isolation method for putative stem/progenitor cells by flow cytometric cell sorting and characterized their potential for differentiation to pancreatic tissue using both in vitro and in vivo protocols. Flow cytometry and the subsequent reverse transcription-polymerase chain reaction and microarray analysis revealed pancreatic epithelial progenitor cells to be highly enriched in the prominin1^highPDGFRβ^– cell population. During in vivo differentiation, these cell populations were able to differentiate into endocrine, exocrine, and ductal tissues, including the formation of an insulin-producing cell cluster. We established the prospective isolation of putative pancreatic epithelial progenitor cells by sorting for prominin1 and PDGFRβ. Since this strategy is based on the cell surface markers common to human and rodents, these findings may lead to the development of new strategies to derive transplantable islet-replacement tissues from human pancreatic stem/progenitor cells.

Disclosure of potential conflicts of interest is found at the end of this article.