Genome integrity, stem cells and hyaluronan

Darżynkiewicz, Zbigniew; Balazs, Endre A.

doi:10.18632/aging.100438

Cited by 33 publications

(31 citation statements)

References 118 publications

(146 reference statements)

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“…Hyaluronan receptors are a generic trait of stem/progenitors and are found in a variety of isoforms resulting from alternative gene splicing . Certain variants form multiprotein complexes with EpCAM, claudins, tetraspanins, and integrins and are associated with metastasis of liver, and other types of cancer .…”

Section: Discussionmentioning

confidence: 99%

Lineage‐dependent effects of aryl hydrocarbon receptor agonists contribute to liver tumorigenesis

Harrill

Parks

Wauthier³

et al. 2015

Hepatology

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Rodent cancer bioassays indicate that the aryl hydrocarbon receptor (AHR) agonist, 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD), causes increases in both hepatocytic and cholangiocytic tumors. Effects of AHR activation have been evaluated on rodent hepatic stem cells (rHpSCs) versus their descendants, hepatoblasts (rHBs), two lineage stages of multipotent, hepatic precursors with overlapping but also distinct phenotypic traits. This was made possible by defining the first successful culture conditions for ex vivo maintenance of rHpScs consisting of a substratum of hyaluronans and Kubota's medium (KM), a serum-free medium designed for endodermal stem/progenitor cells. Supplementation of KM with leukemia inhibitory factor elicited lineage restriction to rHBs. Cultures were treated with various AHR agonists including TCDD, 6-formylindolo-[3,2-b]carbazole (FICZ), and 3-3'-diindolylmethane (DIM) and then analyzed with a combination of immunocytochemistry, gene expression, and high-content image analysis. The AHR agonists increased proliferation of rHpSCs at concentrations producing a persistent AHR activation as indicated by induction of Cyp1a1. By contrast, treatment with TCDD resulted in a rapid loss of viability of rHBs, even though the culture conditions, in the absence of the agonists, were permissive for survival and expansion of rHBs. The effects were not observed with FICZ and at lower concentrations of DIM. Conclusion: Our findings are consistent with a lineage-dependent mode of action for AHR agonists in rodent liver tumorigenesis through selective expansion of rHpSCs in combination with a toxicity-induced loss of viability of rHBs. These lineage-dependent effects correlate with increased frequency of liver tumors. (Hepatology 2015;61:548-560)

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Section: Discussionmentioning

confidence: 99%

Lineage‐dependent effects of aryl hydrocarbon receptor agonists contribute to liver tumorigenesis

Harrill

Parks

Wauthier³

et al. 2015

Hepatology

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“…Adult stem cells reside within specialized microenvironments in which they are kept undifferentiated due to secreted signals from surrounding cells, cell-cell interactions and adhesion to extracellular matrix components [25, 26]. As stem cells divide into more differentiated cells they migrate out of this niche and have access to new cues from the environment, which leads to further differentiation steps [27].…”

Section: Discussionmentioning

confidence: 99%

Human induced pluripotent stem cell differentiation and direct transdifferentiation into corneal epithelial-like cells

Cieślar-Pobuda

Rafat²,

Knoflach

et al. 2016

Oncotarget

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The corneal epithelium is maintained by a small pool of tissue stem cells located at the limbus. Through certain injuries or diseases this pool of stem cells may get depleted. This leads to visual impairment. Standard treatment options include autologous or allogeneic limbal stem cell (LSC) transplantation, however graft rejection and chronic inflammation lowers the success rate over long time. Induced pluripotent stem (iPS) cells have opened new possibilities for treating various diseases with patient specific cells, eliminating the risk of immune rejection. In recent years, several protocols have been developed, aimed at the differentiation of iPS cells into the corneal epithelial lineage by mimicking the environmental niche of limbal stem cells. However, the risk of teratoma formation associated with the use of iPS cells hinders most applications from lab into clinics. Here we show that the differentiation of iPS cells into corneal epithelial cells results in the expression of corneal epithelial markers showing a successful differentiation, but the process is long and the level of gene expression for the pluripotency markers does not vanish completely. Therefore we set out to determine a direct transdifferentiation approach to circumvent the intermediate state of pluripotency (iPS-stage). The resulting cells, obtained by direct transdifferentiation of fibroblasts into limbal cells, exhibited corneal epithelial cell morphology and expressed corneal epithelial markers. Hence we shows for the first time a direct transdifferentiation of human dermal fibroblasts into the corneal epithelial lineage that may serve as source for corneal epithelial cells for transplantation approaches.

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“…HA is a predominant component of intercellular matrix of stem cell niche which protects cells from oxidative DNA damage [27]. It interacts with cells mainly through CD44 and RHAMM receptors [28,29], but cannot crosslink to form hydrogel per se.…”

Section: Hyaluronic Acid (Or Hyaluronan Ha)mentioning

confidence: 99%

The Application of Stem Cell Based Tissue Engineering in Spinal Cord Injury Repair.

Niu¹,

Zeng²

2015

J Tissue Sci Eng

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Spinal Cord Injury (SCI) results in the permanent functional impairment, leading to monoplegia, paraplegia or tetraplegia with tremendous social and economic burden. The intrinsic repair mechanism has been proven to be insufficient. The complex pathophysiology after injury imposes enormous challenging to functional recovery, given the most advanced medical intervention nowadays. Therefore, the development of effective therapeutic strategy for spinal cord injury management is in great need. Here we review a stem cell based tissue engineering approach under preclinical or clinical development for spinal cord injury, with a focus on promoting functional recovery after SCI, aiming to provide some beneficial suggestion on stem cell based tissue engineering design.

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Genome integrity, stem cells and hyaluronan

Cited by 33 publications

References 118 publications

Lineage‐dependent effects of aryl hydrocarbon receptor agonists contribute to liver tumorigenesis

Lineage‐dependent effects of aryl hydrocarbon receptor agonists contribute to liver tumorigenesis

Human induced pluripotent stem cell differentiation and direct transdifferentiation into corneal epithelial-like cells

The Application of Stem Cell Based Tissue Engineering in Spinal Cord Injury Repair.

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