Morphological feature of pancreatic stem cell development and differentiation

초록

Nestin is an intermediate filament protein occurring transiently in early developmental stages in CNS, and known as a marker for neural stem cells (Lendahl et al., 1990: Dahlstrand et al., 1992). This class VI intermediate filament is also transiently expressed in various tissues including pancreas during in the process of development and tissue regeneration (Kachinsky et al., 1994: Wroblewski et al., 1997: Frojdman et al., 1997). Not only embryonic, but also adult stem cells are potential sources for insulin-containing cells. Recently, nestin is used as a stem cell marker for ES cell-derived progenitor cells of insulin secreting beta cells (Lumelsky et al., 2001: Bonner-Weir & Sharma, 2002), leading its possible application for adult pancreatic stem cells. Zulewski et al., (2001) isolated the NIP (nestin-positive islet-derived progenitor) cells as putative adult stem cells for insulin secreting beta cells. Nestin-positive ductal cells induced by neogenic stimulation Pancreatic regeneration has indeed been induced in adult pancreas under particular experimental conditions. Among others, subtotal Px does induce neogenic regeneration of pancreatic tissue. We hypothesized that nestin-positive pancreatic progenitor cells could be developed from the ductal cells in response to neogenic stimulation such as tissue removal by pancreatectomy (Px). Subtotal Px induces immediate neogenic regeneration in rat (Sharma et al., 1999: Bonner-Weir et al., 1983, 1993). In the present study we identified a rich population of nestin cells showing a high replicability in the duct epithelia during the process of duct formation, but not in the pre-differentiated tissue after neogenic stimulation induced by subtotal pancreatectomy. It implies that those nestin positive duct cells could be adult stem cells generated by neogenic motivation and they could differentiate into either exocrine or endocrine cells while losing nestin expression.