The Qatar International Conference on Stem Cell Science and Policy

Over the past few years, GCC countries have witnessed remarkable social and economic growth, which is best reflected in their well-organized and efficient health care systems. With these achievements, a shift in the pattern of disease has become evident. There has been a change in a disease pattern with a falling incidence of communicable diseases, decrease of mortality and morbidity rates of infants and children and a rise in noncommunicable conditions.

Families in GCC states can benefit from new genetic approaches, but these need to be designed to conform with the community beliefs and culture. Presently, GCC communities need help in coping with the changes and challenges that genetic knowledge brings to their lives.

Understanding social beliefs, respect of the traditions set up in an Islamic community, and understanding the psychological difficulties faced by families are essential for acceptance of new technological advances. The difficulties faced by families and proposed solutions are discussed.

Ovarian cancer is a highly metastatic disease. Epithelial ovarian cancer is the most lethal gynecologic malignancy with the majority of cases being diagnosed after the disease has become metastatic. Recent reports have shown that 25% of cancerous cells within tumors have features of cancer stem cells (CSCs). CSCs have been identified on the basis of their ability for self-renewal and to have the capacity to differentiate into cancer cells and also form tumors in animal models. EMT describes a mechanism by which cells lose their epithelial characteristics and acquire more migratory mesenchymal properties. It also seems to have a key role in the acquisition of invasive and migratory properties in many types of carcinoma cells. The aim of this study is to understand the molecular changes and signaling pathways associated with ovarian cancer cell transformation which may lead to the identification of targets for novel therapeutic interventions.

OVCAR-3 and hospicells were cultured in vitro according to standard procedure. OVCAR cells were stained using anti CD133 –prominin-1 and anti CD117-APC and sorted by FACS system as positive and negative. The supernatant of OVCAR CD117+ and CD117- were analyzed by cytokine array And 174 different membrane coupled anti-cytokines along with appropriate controls were studied. The gene expression patterns of OVCAR-3 cultured with supernatant of Hospicells (clone M16) or control cells were analysed and compared by a two-colour topic-defined microarray. The products of microarray consisted of genes related to cytokines, interleukins and growth factors. The up regulated 86 codes genes were analysed by DAVID functional annotation tool.

We demonstrated that OVCAR-3 cell line for several reasons did not appear to be monoclonal. It contains tow subpopulations: one expressing CD117 and the other not. The fact that OVCAR-3 expresses at the same time CD133 and CD117 is indicative of the stem cell nature of this cell line. The cytokines secreted by CD117+ and CD117- were not the same and indicate the different profile of these cells in cell behavior. Analysis was of OVCAR gene array after 8h incubation of Hospicells by DAVID functional annotation tool intricate gpl 130 (IL6 ST) cytokine receptor interaction (IL6, IL11, OSM, LIF, CNTF ligands) and angiogenic factors expression.

We found that OVCAR-3 is apparently a suitable model for studying ovarian cancer stem cells and Epithelial to Mesenchymal Transition in Ovarian Cancer Cells.

Neural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN) which are rich in dopaminergic (DA) neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6%) genes were up-regulated in the hENSC, 4116 (30.4%) genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93%) were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA) differentiation, and to identify the crucial signaling pathways that direct the process of differentiation.

The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells.

Banking of biomedical tissues or information related to them has been conducted around the world for clinical, research and/or commercial purposes. In addition to stem cells in the differentiated tissues such as cord blood and bone marrow, pluripotent stem cells are also subjects of banking. Human embryonic stem cells (hES cells) are one type of these cells, but induced pluripotent stem cells (iPS cells) are now also subjects of banking for various purposes.

In Japan, the Center for iPS Cell Research and Application (CiRA), led by Dr Shinya Yamanaka, was established in 2010 to conduct research on iPS cells. In order to realize iPS cell based therapies, CiRA is now working to establish a new iPS cell bank. The bank aims to establish clinical-grade, HLA-matched iPS cell lines from healthy volunteers and store them to provide for therapeutic or research use. Although some iPS cell banks in Japan or in other countries, including the one in CiRA, are already established, these banks store and provide basically disease-specific iPS cell lines. Therefore, the planned iPS cell bank at CiRA is unique in that it is going to store and provide clinical-grade iPS cells derived from healthy volunteers.

We have been collaborating with researchers at CiRA to establish appropriate procedures for the recruitment of healthy volunteers. We have found that there are a variety of ethical, legal, and social issues (ELSI) that need to be addressed. Since iPS cells are pluripotent stem cells, some ELSI are similar to those already identified in hES cell banks. However, there are other issues that are relatively novel and specific to iPS cells, especially when the donor is a healthy volunteer, not a patient. These ELSI identified arise because: 1. these cells are derived from healthy volunteers; 2. these cells expand infinitely; and 3. the bank deals not only with information such as genome sequence but also with other aspects of the cells.

In this presentation, we will summarize and discuss the ELSI we encountered while establishing the process of healthy-volunteer recruitment for the iPS cell bank.

It has been shown that shear stress plays a critical role in promoting endothelial cell (EC) differentiation from embryonic stem cell (ESC)-derived ECs. However, the underlying mechanisms mediating shear stress effects in this process have yet to be investigated. It has been reported that the glycocalyx component heparan sulfate proteoglycan (HSPG) mediates shear stress mechanotransduction in mature EC.

In this study, we investigated whether cell surface HSPG plays a role in shear stress modulation of EC phenotype. ESC-derived EC were subjected to shear stress (5 dyn/cm(2) ) for 8h with or without heparinase III (Hep III) that digests heparan sulfate. Immunostaining showed that ESC-derived EC surfaces contain abundant HSPG, which could be cleaved by Hep III. We observed that shear stress significantly increased the expression of vascular EC-specific marker genes (vWF, VE-cadherin, PECAM-1. The effect of shear stress on expression of tight junction protein genes (ZO-1, OCLD, CLD5) was also evaluated. Shear stress increased the expression of ZO-1 and CLD5, while it did not alter the expression of OCLD. Shear stress increased expression of vasodilatory genes (eNOS, COX-2), while it decreased the expression of the vasoconstrictive gene ET1. After reduction of HSPG with Hep III, the shear stress-induced expression of vWF, VE-cadherin, ZO-1, eNOS, and COX-2, were abolished, suggesting that shear stress-induced expression of these genes depends on HSPG. These findings indicate for the first time that HSPG is a mechanosensor mediating shear stress-induced EC differentiation from ESC-derived EC cells.