The stromal cell–derived factor-1α/CXCR4 ligand–receptor axis is critical for progenitor survival and migration in the pancreas

Kayali, Ayse G.; Gunst, Kurt Van; Campbell, Iain L.; Stotland, Aleksandr; Kritzik, Marcie; Liu, Guoxun; Flodström‐Tullberg, Malin; Zhang, You Qing; Sarvetnick, Nora

doi:10.1083/jcb.200304153

Cited by 101 publications

(86 citation statements)

References 71 publications

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“…The MEK/ERK pathway was found necessary and sufficient to induce mitogenesis in adult human duct cells. The MEK/ERK pathway is also activated to influence proliferation of pancreatic duct cells during pancreas regeneration in RIP-IFNgamma transgenic mice by stromal cell-derived factor-1alpha 26 and following overexpression of amphiregulin 27 in mice.…”

Section: Discussionmentioning

confidence: 99%

EGF-induced proliferation of adult human pancreatic duct cells is mediated by the MEK/ERK cascade

Rescan

Bras

Lefebvre

et al. 2005

Laboratory Investigation

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Human postnatal pancreatic duct cells are a potential source of new beta cells. Factors regulating proliferation of human pancreatic duct cells in vitro are unknown. In several other cell types, this process is influenced by ligands of the ErbB receptor family. The expression and functionality of the ErbB family members and their possible role in duct cell proliferation were determined. In cultured adult human pancreatic duct cells the different members of the ErbB family (ErbB1-4) were present at transcript and protein level. Stimulation of the duct cells with epidermal growth factor (EGF) and betacellulin results in Tyr-phosphorylation of ErbB1 and ErbB2, followed by activation of Shc, MEK1/2 and ERK1/2. Duct cells with activated ErbB signaling changed morphology and motility. EGF induced proliferation of a fraction of the duct cells and treatment with PD98059 prevented Ki67 expression in EGF-supplemented cells. When transduced with recombinant adenovirus expressing constitutively activated MEK1, duct cells proliferate and spread even in the absence of EGF. Importantly, the adult human duct cells retain their capacity to recapitulate ngn3-induced embryonic (neuro)endocrine differentiation after proliferation. Therefore, the present data support a possible role for human adult pancreatic duct cells, following expansion and transdifferentiation, as a source of insulin by transplantation to type I diabetes patients.

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Section: Discussionmentioning

confidence: 99%

EGF-induced proliferation of adult human pancreatic duct cells is mediated by the MEK/ERK cascade

Rescan

Bras

Lefebvre

et al. 2005

Laboratory Investigation

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“…19 Besides these important functions, SDF-1 has also growth-promoting effects, 34 participates to angiogenesis, 35 and is involved in the differentiation of progenitor cells. 19,36 Stromal cellderived factor-1 binding to heparan sulfates at the outer surface of cell membranes increases its local concentration and facilitates receptor occupancy. 37 To establish a role of SDF-1 in hepatic regeneration from oval cells, rats were injected with fucoidan.…”

Section: Discussionmentioning

confidence: 99%

Expression of Stromal Cell-Derived Factor-1 and of Its Receptor CXCR4 in Liver Regeneration from Oval Cells in Rat

Mavier

Martin

Couchie

et al. 2004

The American Journal of Pathology

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Stromal cell-derived factor-1 is a chemokine that plays a major role during embryogenesis. Since stromal cell-derived factor-1 and its unique receptor CXCR4 are involved in the differentiation of progenitor cells, we studied the expression of this chemokine and of its receptor in hepatic regeneration from precursor oval cells. Hepatic regeneration was induced by treating rats with 2-acetylaminofluorene, and followed by partial hepatectomy. Oval cell accumulation, which predominated in periportal regions, reached a maximum at days 9 to 14 after hepatectomy and declined thereafter. Oval cells strongly expressed stromal cell-derived factor-1 protein and mRNA. CXCR4 mRNA hepatic level paralleled the number of oval cells and in situ hybridization showed CXCR4 mRNA expression by these cells. Treatment of rats with fucoidan, a sulfated polysaccharide which binds to stromal cell-derived factor-1 and blocks its biological effects, markedly decreased oval cell accumulation in five of the seven treated rats. In conclusion, our data demonstrate an expression of stromal cellderived factor-1 and of its receptor CXCR4 in oval cells during hepatic regeneration and strongly suggest that stromal cell-derived factor-1 stimulates the proliferation of these precursor cells through an autocrine/paracrine pathway.

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“…Currently, common procedures for preparation of single-cell suspensions from adult mouse pancreata include subjecting the excised tissue to digestive fluid supplemented with collagenase alone or a combination of collagenase and trypsin at 37 °C, followed by mechanical shearing (Kayali et al, 2003;Suzuki et al, 2004;Inada et al, 2008). Collagenase provides gentle, selective digestion of the intercellular matrix, but is unable to completely disassociate organ tissue into single cells (Gross et al, 1974).…”

Section: Introductionmentioning

confidence: 99%

Complete disassociation of adult pancreas into viable single cells through cold trypsin-EDTA digestion

Peng

Zhang

et al. 2013

J. Zhejiang Univ. Sci. B

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Abstract:The in vitro isolation and analysis of pancreatic stem/progenitor cells are necessary for understanding their properties and function; however, the preparation of high-quality single-cell suspensions from adult pancreas is prerequisite. In this study, we applied a cold trypsin-ethylenediaminetetraacetic acid (EDTA) digestion method to disassociate adult mouse pancreata into single cells. The yield of single cells and the viability of the harvested cells were much higher than those obtained via the two commonly used warm digestion methods. Flow cytometric analysis showed that the ratio of ductal or BCRP1-positive cells in cell suspensions prepared through cold digestion was consistent with that found in vivo. Cell culture tests showed that pancreatic epithelial cells prepared by cold digestion maintained proliferative capacity comparable to those derived from warm collagenase digestion. These results indicate that cold trypsin-EDTA digestion can effectively disassociate an adult mouse pancreas into viable single cells with minimal cell loss, and can be used for the isolation and analysis of pancreatic stem/progenitor cells.

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The stromal cell–derived factor-1α/CXCR4 ligand–receptor axis is critical for progenitor survival and migration in the pancreas

Cited by 101 publications

References 71 publications

EGF-induced proliferation of adult human pancreatic duct cells is mediated by the MEK/ERK cascade

EGF-induced proliferation of adult human pancreatic duct cells is mediated by the MEK/ERK cascade

Expression of Stromal Cell-Derived Factor-1 and of Its Receptor CXCR4 in Liver Regeneration from Oval Cells in Rat

Complete disassociation of adult pancreas into viable single cells through cold trypsin-EDTA digestion

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