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Edinburgh, United Kingdom

Courtney A.,Roslin Cells Ltd
Regenerative Medicine | Year: 2011

Scotland is shaping up as Europe's 'go-to' place to translate cell therapy research from the laboratory into the clinic. While continuing to punch above its weight in fundamental research, the resources for translating research to clinical application are perhaps its main attraction for the international stem cell research community. © 2011 Future Medicine Ltd. Source

Anderson R.A.,University of Edinburgh | Bayne R.A.L.,University of Edinburgh | Gardner J.,University of Edinburgh | De Sousa P.A.,University of Edinburgh | De Sousa P.A.,Roslin Cells Ltd
Fertility and Sterility | Year: 2010

Objective: To investigate a role for brain-derived neurotrophic factor (BDNF) in human oocyte maturation. Design: Prospective study. Setting: Research institute. Patients: Women undergoing laparoscopic sterilization. Intervention(s): Small antral follicle cumulus-oocyte complexes (COCs) were matured in vitro (IVM) to metaphase II (MII) in media with hormones (H; FSH, LH, E2), serum replacement (SR), BDNF, or blocking antibodies to BDNF (BDNF/AB and TrkB/Fc), and activated. Main Outcome Measure(s): The COCs were analyzed for expression of neurotrophin ligands/receptors and cumulus genes (HAS2, TNFAlP6, PTGS2, GREM1) by reverse transcription-polymerase chain reaction (RT-PCR), cumulus expansion, maturation to MII, and parthenogenetic embryo development. Result(s): The BDNF and truncated TrkB receptor were expressed in cumulus and mature oocytes. There was no difference in MII yields after IVM in control (H + SR) versus H + BDNF, H + SR + BDNF, or BDNF + SR media. However, both BDNF/AB and TrkB/Fc improved MII yields. After activation, normal cleavage was highest in H + SR (38%), whereas blocking antibodies yielded the highest abnormal cleavage (BDNF/AB 68%; TrkB/Fc 57%). Failure to cleave was highest in H + BDNF + SR (92%). Only H + SR yielded morulae/blastocysts (6%). Expression of GREM1 in cumulus increased after IVM in H + BDNF versus H + SR or in vivo maturation. Conclusion(s): The BDNF signaling within COCs influences oocyte maturation and early embryogenesis. © 2010 American Society for Reproductive Medicine. Source

Murdoch A.,Newcastle University | Braude P.,Kings College London | Courtney A.,Roslin Cells Ltd | Brison D.,University of Manchester | And 5 more authors.
Stem Cell Reviews and Reports | Year: 2012

The donation of human embryos for the derivation of embryonic stem cell lines that may be used in the development of therapeutic products raises more complex ethical, practical and regulatory problems than the donation of embryos for non-clinical research. This review considers these issues and offers recommendations for good practice. © 2011 Springer Science+Business Media, LLC. Source

Sneddon S.F.,University of Manchester | Desousa P.A.,University of Edinburgh | Desousa P.A.,Roslin Cells Ltd | Arnesen R.E.,University of Manchester | And 3 more authors.
Fertility and Sterility | Year: 2011

Objective: To create developmentally competent embryos from failed-to-fertilize oocytes for use in infertility research and human embryonic stem cell derivation. Design: Attempts to recover developmental potential of failed-to-fertilize oocytes were made by using either parthenogenetic activation or reinsemination by intracytoplasmic sperm injection. Resulting embryos were cultured to various stages up to and including blastocyst, and single embryos exhibiting normal development were analyzed for gene expression by quantitatively profiling representative transcripts. Setting: Hospital-based assisted reproductive technology laboratory and University academic laboratories. Patient(s): One hundred sixty-five couples undergoing assisted fertility treatment. Intervention(s): Metaphase II stage oocytes were either parthenogenetically activated or reinseminated with donor sperm, then allowed to develop up to and including the blastocyst stage. Main Outcome Measure(s): Gene expression analysis was performed on oocytes and embryos by quantitative reverse transcriptase-polymerase chain reaction for markers of developmental competence. Result(s): Fertilization occurred in 65% of the activated or reinseminated oocytes, which resulted in a blastocyst formation rate of 8%. Evaluation of a number of developmentally important genes in those embryos exhibiting normal development revealed profile and levels of expression similar to control embryos. One blastocyst from an activated oocyte yielded a novel pluripotent stem cell line indistinguishable from those derived from embryos surplus to infertility treatment. Conclusion(s): Clinically unusable oocytes represent a valuable alternative source of normal human embryos for human infertility and stem cell research without conflicting with patient treatment. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc. Source

Faulkner-Jones A.,Heriot - Watt University | Fyfe C.,Roslin Cellab Ltd | Cornelissen D.-J.,Heriot - Watt University | Gardner J.,Roslin Cellab Ltd | And 5 more authors.
Biofabrication | Year: 2015

We report the first investigation into the bioprinting of human induced pluripotent stem cells (hiPSCs), their response to a valve-based printing process as well as their post-printing differentiation into hepatocyte-like cells (HLCs). HLCs differentiated from both hiPSCs and human embryonic stem cells (hESCs) sources were bioprinted and examined for the presence of hepatic markers to further validate the compatibility of the valve-based bioprinting process with fragile cell transfer. Examined cells were positive for nuclear factor 4 alpha and were demonstrated to secrete albumin and have morphology that was also found to be similar to that of hepatocytes. Both hESC and hiPSC lines were tested for post-printing viability and pluripotency and were found to have negligible difference in terms of viability and pluripotency between the printed and non-printed cells. hESC-derived HLCs were 3D printed using alginate hydrogel matrix and tested for viability and albumin secretion during the remaining differentiation and were found to be hepatic in nature. 3D printed with 40-layer of HLC-containing alginate structures reached peak albumin secretion at day 21 of the differentiation protocol. This work demonstrates that the valve-based printing process is gentle enough to print human pluripotent stem cells (hPSCs) (both hESCs and hiPSCs) while either maintaining their pluripotency or directing their differentiation into specific lineages. The ability to bioprint hPSCs will pave the way for producing organs or tissues on demand from patient specific cells which could be used for animal-free drug development and personalized medicine. © 2015 IOP Publishing Ltd. Source

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