North East England Stem Cell Institute

Newcastle upon Tyne, United Kingdom

North East England Stem Cell Institute

Newcastle upon Tyne, United Kingdom

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Britton K.M.,Northumbria University | Eyre R.,Northumbria University | Harvey I.J.,Northumbria University | Stemke-Hale K.,University of Houston | And 4 more authors.
Cancer Letters | Year: 2012

Recurrent metastatic breast cancer may arise in part due to the presence of drug resistant adult stem cells such as Side Population (SP) cells, whose phenotype has been demonstrated to be due to the expression of ABCG2. We hypothesised that SP may be identified in Fine Needle Aspirates (FNAs) and their presence may be determined by expression of ABCG2 in breast tumours. SP and non-side population cells (NSP) were isolated using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux and analysed for expression of ABCG2 and chemoresistance. FNA samples used in SP analysis were matched with paraffin-embedded tissue which was used in immunohistochemical analysis to assess ABCG2 expression. Results were correlated to the pathobiology of the tumour. MCF7 and MDA-MB-231 cell lines contain SP cells. MCF7 SP have increased expression of ABCG2 and increased resistance to mitoxantrone compared to NSP cells. The presence of SP in FNAs were significantly associated with ER-negative (. p=. 0.008) and with triple negative breast cancers (. p=. 0.011) which were also found to have a significant increase in ABCG2 protein expression. ABCG2 transcript was detected in some but not all SP cell populations isolated from FNA samples. © 2012 Elsevier Ireland Ltd.

Jurga M.,Cell Therapy Research Institute CTI Lyon | Forraz N.,Cell Therapy Research Institute CTI Lyon | Basford C.,Cell Therapy Research Institute CTI Lyon | Basford C.,North East England Stem Cell Institute | And 8 more authors.
Stem Cells and Development | Year: 2012

Several innovative therapies with human umbilical cord blood stem cells (SCs) are currently developing to treat central nervous system (CNS) diseases. It has been shown that cord blood contains multipotent lineage-negative (LinNEG) SCs capable of neuronal differentiation. Clinically useful cord blood samples are stored in different biobanks worldwide, but the content and neurogenic properties of LinNEG cells are unknown. Here we have compared 5 major methods of blood processing: Sepax, Hetastarch, plasma depletion, Prepacyte-SC, and density gradient. We showed that Sepax-processed blood units contained 10-fold higher number of LinNEG cells after cryopreservation in comparison to all other methods. We showed in this study that multipotent SCs derived from fresh and frozen cord blood samples could be efficiently induced in defined serum-free medium toward neuronal progenitors (NF200+, Ki67+). During neuronal differentiation, the multipotent SCs underwent precise sequential changes at the molecular and cellular levels: Oct4 and Sox2 downregulation and Ngn1, NeuN, and PSD95 upregulation, similar to neurogenesis process in vivo. We expect that data presented here will be valuable for clinicians, researchers, biobanks, and patients and will contribute for better efficacy of future clinical trials in regeneration of CNS. © 2012 Mary Ann Liebert, Inc.

Eyre R.,Northumbria University | Harvey I.,Northumbria University | Stemke-Hale K.,University of Houston | Lennard T.W.J.,Northumbria University | And 3 more authors.
Tumor Biology | Year: 2014

The majority of deaths in ovarian cancer are caused by recurrent metastatic disease which is usually multidrug resistant. This progression has been hypothesised to be due in part to the presence of cancer stem cells, a subset of cells which are capable of self-renewal and are able to survive chemotherapy and migrate to distant sites. Side population (SP) cells, identified by the efflux of the DNA-binding dye Hoechst 33342 through ATP-binding cassette (ABC) transporters, are a known adult stem cell group and have been suggested as a cancer stem cell in various cancers. Despite the identification of SP cells in cancer cell lines and patient samples, little attention has been paid to the identification of specific ABC transporters within this cell fraction which efflux Hoechst dye and thus may facilitate drug resistance. In this study, we demonstrate that SP cells can be detected in both ovarian cancer cell lines and ascitic fluid samples, and these SP cells possess stem cell and drug resistance properties. We show that ABCB1 is the functioning ABC transporter in ovarian cancer cell lines, and expression of ABCB1 is associated with a paclitaxel-resistant phenotype. Moreover, silencing of ABCB1 using a specific morpholino oligonucleotide results in an inhibition of the SP phenotype and a sensitising of ovarian cancer cell lines to paclitaxel. ABCB1 should therefore be considered as a therapeutic target in ovarian cancer. © International Society of Oncology and BioMarkers (ISOBM) 2014

PubMed | North East England Stem Cell Institute
Type: Journal Article | Journal: Drug discovery today | Year: 2010

Transparency of the cornea on the front surface of the eye is essential for vision. A variety of blinding ocular surface diseases involve the cornea. This review focusses on vision loss caused by disruption of the integrity and function of the outermost corneal layer (the epithelium) and the stem-cell-based therapeutic strategies in use and under development to restore sight in affected patients.

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