Laminin-1 and epidermal growth factor family members co-stimulate fetal pancreas cell proliferation and colony formation

Jiang, Fuming; Harrison, Leonard C.

doi:10.1111/j.1432-0436.2005.07301002.x

Cited by 24 publications

(18 citation statements)

References 26 publications

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“…We first demonstrated in vitro that bone morphogenetic proteins-2, -4, -5 and -6, members of the transforming growth factor β superfamily, can promote the proliferation of pancreatic precursors and the development of pancreatic cystic epithelial colonies containing β cells (Jiang et al, 2002;Jiang and Harrison, 2005a), a process partially recapitulating an in vivo developmental stage. In addition, we also found that various isoforms of epidermal growth factors can stimulate colony formation (Jiang and Harrison, 2005b). These data indicate that extracellular signalling molecules, including various families of growth factors, modulate fate changes of pancreas precursor/stem cells.…”

Section: Psc May House In Ductal Epitheliumsupporting

confidence: 60%

Pancreatic Stem Cells: Unresolved Business

Jiang¹,

Morahan²

2011

Stem Cells in Clinic and Research

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Section: Psc May House In Ductal Epitheliumsupporting

confidence: 60%

Pancreatic Stem Cells: Unresolved Business

Jiang¹,

Morahan²

2011

Stem Cells in Clinic and Research

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“…Although, to date, most of the supporting evidence for this concept has been derived from animal (mainly rodent) studies, the results of the present investigation suggest that similar regulatory and/or trophic influences, exerted by the ductal epithelia, may be crucial for appropriate and sustained human beta cell function. Soluble mediators such as IGF-1 and -2 and the epidermal growth factor (EGF) family have been implicated in beta cell survival and replication [38][39][40][41], and ductal epithelial cells may provide an additional source of these regulatory hormones in the post-isolation environment [41]. Additionally, components of the ECM are vital for appropriate pancreatic development, and several integrin receptors and their associated ligands, including laminin, fibronectin and collagen I, are produced in ductal cells [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

“…Soluble mediators such as IGF-1 and -2 and the epidermal growth factor (EGF) family have been implicated in beta cell survival and replication [38][39][40][41], and ductal epithelial cells may provide an additional source of these regulatory hormones in the post-isolation environment [41]. Additionally, components of the ECM are vital for appropriate pancreatic development, and several integrin receptors and their associated ligands, including laminin, fibronectin and collagen I, are produced in ductal cells [41][42][43]. Whether the actions of one or several of these factors underlie the improved beta cell function in our co-culture models will thus form the basis of future research.…”

Section: Discussionmentioning

confidence: 99%

Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system

et al. 2009

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Aims/hypothesis Loss of the trophic support provided by surrounding non-endocrine pancreatic cell populations underlies the decline in beta cell mass and insulin secretory function observed in human islets following isolation and culture. This study sought to determine whether restoration of regulatory influences mediated by ductal epithelial cells promotes sustained beta cell function in vitro. Methods Human islets were isolated according to existing protocols. Ductal epithelial cells were harvested from the exocrine tissue remaining after islet isolation, expanded in monolayer culture and characterised using fluorescence immunocytochemistry. The two cell types were co-cultured under conventional static culture conditions or within a rotational cell culture system. The effect of co-culture on islet structural integrity, beta cell mass and insulin secretory capacity was observed for 10 days following isolation. Results Human islets maintained under conventional culture conditions exhibited a characteristic loss in structural integrity and functional viability as indicated by a diminution of glucose responsiveness. By contrast, co-culture of islets with ductal epithelial cells led to preserved islet morphology and sustained beta cell function, most evident in co-cultures held within the rotational cell culture system, which showed a significantly (p<0.05) greater insulin secretory response to elevated glucose compared with control islets. Similarly, insulin/protein ratio data suggested that the presence of ductal epithelial cells is beneficial for the maintenance of beta cell mass. Conclusions/interpretation The data indicate a supportive role for ductal epithelial cells in islet viability. Further characterisation of the regulatory influences may lead to novel strategies to improve long-term beta cell function both in vitro and following islet transplantation.

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“…Of the cDNA, 75 ng were amplified by PCR in 1.1×ReddyMix PCR Master Mix (ABgene, Epsom, UK) containing 50 ng of each primer pair. Details of the mouse primers [20] are found in the accompanying ESM.…”

Section: Methodsmentioning

confidence: 99%

Betacellulin inhibits amylase and glucagon production and promotes beta cell differentiation in mouse embryonic pancreas

Thowfeequ

Ralphs

et al. 2007

Diabetologia

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Aims/hypothesis Betacellulin, a member of the epidermal growth factor family, is expressed in the pancreas and is thought to regulate differentiation of beta cells during development. The aim of the present study was to investigate the effects of exogenous betacellulin on the development of the mouse embryonic pancreas. Materials and methods We used an in vitro culture model system based on the isolation and culture of the dorsal embryonic pancreas from day 11.5 embryos. Cultures were treated for up to 10 days with 10 ng/ml betacellulin and then analysed for changes in the expression of pancreatic exocrine, endocrine and ductal markers. Results Pancreases developed in culture and expressed the full complement of exocrine (both acinar and ductal) and endocrine cell types. Betacellulin enhanced branching morphogenesis and the proliferation of mesenchyme, increased Pdx1 and insulin production and inhibited the production of the exocrine cell marker amylase and the endocrine hormone glucagon. Conclusions/interpretation These results suggest betacellulin has distinct and separate effects on exocrine, endocrine and ductal differentiation. In the future, betacellulin could perhaps be utilised to increase the production of beta cells from embryonic pancreatic tissue for therapeutic transplantation.

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Laminin-1 and epidermal growth factor family members co-stimulate fetal pancreas cell proliferation and colony formation

Cited by 24 publications

References 26 publications

Pancreatic Stem Cells: Unresolved Business

Pancreatic Stem Cells: Unresolved Business

Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system

Betacellulin inhibits amylase and glucagon production and promotes beta cell differentiation in mouse embryonic pancreas

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