Endodermal progenitor cells isolated from mouse pancreas

Samuelson, Lisa; Wright, Natasha R.; Gerber, David A.

doi:10.4236/scd.2011.13005

Cited by 4 publications

(2 citation statements)

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“…Progenitors isolated from mice are found to bear several surface markers. For instance, Samuelson et al [37], showed that the highly proliferative pancreatic progenitor population isolated from mice has been found to express stem cells antigen 1- (Sca-1). Another study showed the presence of Nestin positive multipotent progenitor cells in the centrilobular ducts of the adult rat pancreas [38].…”

Section: Origin Of Pancreatic Cancer Stem Cell Hypothesismentioning

confidence: 99%

A concise review on the current understanding of pancreatic cancer stem cells

Vaz¹,

Ponnusamy²,

Seshacharyulu³

et al. 2014

J Cancer Stem Cell Res

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Several evidences suggest that a small population of cells known as cancer stem cells (CSCs) or tumor initiating stemlike cells within a tumor is capable of tumor initiation, maintenance and propagation. Recent publications have supported the existence of CSCs in pancreatic tumors. The pancreatic stem/progenitor cells, which express self-renewal markers, are identified to be present in the peribiliary gland. Based on the CSC hypothesis, mutations can lead to the transformation of stem/progenitor cells or differentiated cells into CSCs. The pancreatic CSCs express a wide array of markers such as CD44, CD24, ESA, CD133, c-MET, CXCR4, PD2/Paf1 and ALDH1. The CSCs are isolated based on surface markers or by other methods such as ALDEFLOUR assay or Hoechst 33342 dye exclusion assay. The isolated cells are further characterized by in vitro and in vivo tumorigenic assays. The most important characteristics of CSCs are its ability to self-renew and impart drug resistance towards chemotherapy. Moreover, these distinct cells display alteration of signaling pathways pertaining to CSCs such as Notch, Wnt and Shh to maintain the selfrenewal process. Failure of cancer treatment could be attributed to the therapy resistance exhibited by the CSCs. Metastasis and drug resistance in pancreatic cancer is associated with epithelial to mesenchymal transition (EMT). Furthermore, mucins, the high molecular weight proteins are found to be associated with pancreatic CSCs and EMT. Understanding the underlying molecular pathways that aid in the metastatic and drug resistant nature of these distinct cells will aid in targeting these cells. Overall, this review focuses on the various aspects of pancreatic adult/stem progenitors, CSC hypothesis, its markers, pathways, niche, EMT and novel therapeutic drugs used for the elimination of pancreatic CSCs.

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Section: Origin Of Pancreatic Cancer Stem Cell Hypothesismentioning

confidence: 99%

A concise review on the current understanding of pancreatic cancer stem cells

Vaz¹,

Ponnusamy²,

Seshacharyulu³

et al. 2014

J Cancer Stem Cell Res

View full text Add to dashboard Cite

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“…Determined stem cells for pancreatic cell therapies have not been considered an option based on evidence that there are no or only rare pancreatic stem cells in postnatal tissues []. The few studies in which OCT4 + and SOX2 + multipotent stem cells have been identified in adult pancreas have indicated also their rarity []. Instead, the postnatal pancreas has long been thought to contain only committed progenitors, found in pancreatic ducts [] and, more recently, in pancreatic duct glands (PDGs) by Thayer and associates [].…”

Section: Introductionmentioning

confidence: 99%

Biliary tree stem cells, precursors to pancreatic committed progenitors: Evidence for possible life-long pancreatic organogenesis

et al. 2013

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Peribiliary glands (PBGs) in bile duct walls, and pancreatic duct glands (PDGs) associated with pancreatic ducts, in humans of all ages, contain a continuous, ramifying network of cells in overlapping maturational lineages. We show that proximal (PBGs)-to-distal (PDGs) maturational lineages start near the duodenum with cells expressing markers of pluripotency (NANOG,OCT4,SOX2), proliferation (Ki67), self-replication (SALL4), and early hepato-pancreatic commitment (SOX9,SOX17,PDX1,LGR5), transitioning to PDG cells with no expression of pluripotency or self-replication markers, maintenance of pancreatic genes (PDX1), and expression of markers of pancreatic endocrine maturation (NGN3,MUC6,insulin). Radial-axis lineages start in PBGs near the ducts’ fibromuscular layers with stem cells and end at the ducts’ lumens with cells devoid of stem cell traits and positive for pancreatic endocrine genes. Biliary tree-derived cells behaved as stem cells in culture under expansion conditions, culture plastic and serum-free Kubota’s Medium, proliferating for months as undifferentiated cells, whereas pancreas-derived cells underwent only ∼8-10 divisions, then partially differentiated towards an islet fate. Biliary tree-derived cells proved precursors of pancreas’ committed progenitors. Both could be driven by 3-dimensional conditions, islet-derived matrix components and a serum-free, hormonally defined medium for an islet fate (HDM-P), to form spheroids with ultrastructural, electrophysiological and functional characteristics of neoislets, including glucose regulatability. Implantation of these neoislets into epididymal fat pads of immuno-compromised mice, chemically rendered diabetic, resulted in secretion of human C-peptide, regulatable by glucose, and able to alleviate hyperglycemia in hosts. The biliary tree-derived stem cells and their connections to pancreatic committed progenitors constitute a biological framework for life-long pancreatic organogenesis.

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