The Quest for Tissue Stem Cells in the Pancreas and Other Organs, and their Application in Beta-Cell Replacement

Houbracken, Isabelle; Bouwens, Luc

doi:10.1900/rds.2010.7.112

Cited by 17 publications

(9 citation statements)

References 88 publications

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“…Since CSC are very similar to non-malignant stem cells, it is suggested that CSC can be created by oncogenic transformation of tissue-specific stem cells [270,271]. However, in it is still unclear whether an adult stem cell pool resides in the pancreas [272], posing the possibility that there may be an alternative source for pancreatic CSC. Besides, evidence indicates that CSC are not necessarily derived from normal stem cells.…”

Section: Pancreatic Cancer Stem Cells and Emtmentioning

confidence: 99%

Cancer Stem Cells, EMT, and Developmental Pathway Activation in Pancreatic Tumors

Hindriksen

Bijlsma

2012

Cancers

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Pancreatic cancer is a disease with remarkably poor patient survival rates. The frequent presence of metastases and profound chemoresistance pose a severe problem for the treatment of these tumors. Moreover, cross-talk between the tumor and the local micro-environment contributes to tumorigenicity, metastasis and chemoresistance. Compared to bulk tumor cells, cancer stem cells (CSC) have reduced sensitivity to chemotherapy. CSC are tumor cells with stem-like features that possess the ability to self-renew, but can also give rise to more differentiated progeny. CSC can be identified based on increased in vitro spheroid- or colony formation, enhanced in vivo tumor initiating potential, or expression of cell surface markers. Since CSC are thought to be required for the maintenance of a tumor cell population, these cells could possibly serve as a therapeutic target. There appears to be a causal relationship between CSC and epithelial-to-mesenchymal transition (EMT) in pancreatic tumors. The occurrence of EMT in pancreatic cancer cells is often accompanied by re-activation of developmental pathways, such as the Hedgehog, WNT, NOTCH, and Nodal/Activin pathways. Therapeutics based on CSC markers, EMT, developmental pathways, or tumor micro-environment could potentially be used to target pancreatic CSC. This may lead to a reduction of tumor growth, metastatic events, and chemoresistance in pancreatic cancer.

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Section: Pancreatic Cancer Stem Cells and Emtmentioning

confidence: 99%

Cancer Stem Cells, EMT, and Developmental Pathway Activation in Pancreatic Tumors

Hindriksen

Bijlsma

2012

Cancers

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“…The generation of functional pancreatic beta-cells to compensate for the short supply of donor human islets has long been regarded as a potential solution for the treatment of diabetes 39 . To this goal, great efforts have been made to generate functional beta-cells from non-beta cell sources, e.g.…”

Section: Discussionmentioning

confidence: 99%

PNA lectin for purifying mouse acinar cells from the inflamed pancreas

Xiao

Fischbach

Fusco

et al. 2016

Sci Rep

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Better methods for purifying human or mouse acinar cells without the need for genetic modification are needed. Such techniques would be advantageous for the specific study of certain mechanisms, such as acinar-to-beta-cell reprogramming and pancreatitis. Ulex Europaeus Agglutinin I (UEA-I) lectin has been used to label and isolate acinar cells from the pancreas. However, the purity of the UEA-I-positive cell fraction has not been fully evaluated. Here, we screened 20 widely used lectins for their binding specificity for major pancreatic cell types, and found that UEA-I and Peanut agglutinin (PNA) have a specific affinity for acinar cells in the mouse pancreas, with minimal affinity for other major pancreatic cell types including endocrine cells, duct cells and endothelial cells. Moreover, PNA-purified acinar cells were less contaminated with mesenchymal and inflammatory cells, compared to UEA-I purified acinar cells. Thus, UEA-I and PNA appear to be excellent lectins for pancreatic acinar cell purification. PNA may be a better choice in situations where mesenchymal cells or inflammatory cells are significantly increased in the pancreas, such as type 1 diabetes, pancreatitis and pancreatic cancer.

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“…Those of Swenson [] found that acinar cells derive from a single stem cell, whereas islets derive from more than one []. Importantly, stem cells are found in postnatal liver [] but are very rare in postnatal pancreas []. This paradox has been clarified recently with the discovery that pancreatic stem cells are not in the pancreas but rather in the biliary tree, particularly in the hepato‐pancreatic common duct [].…”

Section: Epithelial–mesenchymal Maturational Lineagesmentioning

confidence: 99%

Concise review: Clinical programs of stem cell therapies for liver and pancreas

et al. 2013

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Regenerative medicine is transitioning into clinical programs utilizing stem/progenitor cell therapies for repair of damaged organs. We summarize those for liver and pancreas, organs that share endodermal stem cell populations, biliary tree stem cells (hBTSCs), located in peribiliary glands: they are precursors to hepatic stem/progenitors in canals of Hering and to committed progenitors in pancreatic duct glands. They give rise to maturational lineages along a radial axis within bile duct walls and a proximal-to-distal axis starting at the duodenum and ending with mature cells in the liver or pancreas. Clinical trials have been ongoing for years assessing effects of fetal-liver-derived hepatic stem/progenitors transplanted into the hepatic artery of patients with various liver diseases. Immunosuppression was not required. Control subjects, those given standard of care for a given condition, all died within a year or deteriorated in their liver functions. Subjects transplanted with 100–150 million hepatic stem/progenitor cells had improved liver functions and survival extending for several years. Full evaluations of safety and efficacy of transplants are still in progress. Determined stem cell therapies for diabetes utilizing hBTSCs remain to be explored but are likely to occur following ongoing preclinical studies. In addition, mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are being used for patients with chronic liver conditions or with diabetes. MSCs have demonstrated significant effects through paracrine signaling of trophic and immune-modulatory factors, and there is limited evidence for inefficient lineage restriction into mature parenchymal or islet cells. HSCs’ effects are primarily via modulation of immune mechanisms.

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The Quest for Tissue Stem Cells in the Pancreas and Other Organs, and their Application in Beta-Cell Replacement

Cited by 17 publications

References 88 publications

Cancer Stem Cells, EMT, and Developmental Pathway Activation in Pancreatic Tumors

Cancer Stem Cells, EMT, and Developmental Pathway Activation in Pancreatic Tumors

PNA lectin for purifying mouse acinar cells from the inflamed pancreas

Concise review: Clinical programs of stem cell therapies for liver and pancreas

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