A fourth challenge is that the high level of

A fourth challenge is that the high level of regulatory variation across countries necessitates far-reaching forms of scientific self-governance, training and procedural adjustments in participating clinical trial sites (Rosemann, 2014b). A central reason for this is, that the existence of regulatory differences between national jurisdictions is reflected in contrasts of clinical research practices and methodologies, at the level of local medical institutions. In many countries, moreover, knowledge on the conduct of systematized controlled stem Atractyloside Dipotassium Salt trials is often limited among clinical researchers (Li et al., 2014). These disparities between and also within local hospitals form a clear threat to the scientific integrity of international stem cell trials (OECD, 2011). As a result, intensive forms of staff training and adjustments of local clinical research practices are necessary, so that standardized research protocols can be implemented (Ravinetto et al., 2013). Standardization requires, furthermore, the implementation of reliable monitoring and control infrastructures. For academic investigators and small-to-mid size companies the performances of these tasks pose a significant organizational and financial burden (Keirstead, 2012). Unless sufficient funding for these forms of education and scientific self-governance is acquired, multi-center international stem cell trials cannot be conducted.
The need for an international support structure The International Society of Stem Cell Research (ISSCR) has in 2010 called for the need to harmonize regulations for the clinical translation and commercialization of stem cell-based products and therapies (Martell et al., 2010). However, in 2014 the global regulatory landscape for clinical stem cell research remains as diverse as before. This situation continues to pose problems to the organization of transnational stem cell trials. What is needed in order to improve this situation is the creation of an international support structure, through which the organizational challenges of multi-country stem cell trials can be systematically addressed. International bodies such as the ISSCR or the International Stem Cell Forum have until now focused primarily on the development of guidelines, best practice standards and various types of recommendation. These documents have concentrated on crucial aspects of the clinical translation process, including the collection, derivation, storage and clinical application of stem cells, as well as intellectual property rights, commercialization, industry engagement and ethical issues of stem cell research (Isasi, 2012). However, a support structure that specifically addresses the regulatory and organizational challenges of multi-country stem cell trials has so far not yet been developed. Such a scheme could encompass five elements:
Conclusions
Conflict of interest
Acknowledgments This article has benefitted from two research grants. A grant of the UK Economic and Social Research Council: grant RES-062-23-2990; and a grant of the European Research Council: grant ERC-2011-StG_20101124. Thanks to Margaret Sleeboom-Faulkner, Prasanna Patra and my colleagues at the Centre for Bionetworking as well as SPRU at the University of Sussex.
Introduction Understanding the resident stem cell populations of the bile duct system is important for both basic biology and developing therapeutic strategies to treat bile duct diseases. The bile duct system is divided into IHBD and extrahepatic bile duct (EHBD) systems. The EHBD system consists of the common hepatic duct, gallbladder, cystic duct and the common bile duct (CBD) (Hand, 1973; Cardinale et al., 2010). The gallbladder stores bile while modifying its content and concentration (Nakanuma et al., 1997; Frizzell and Heintze, 1980). There is a paucity of data characterizing stem cells in both adult and fetal human gallbladders. In addition, the differences between IHBD and EHBD cells are not well understood. The EHBD system, the liver and the ventral pancreas develop from the posterior ventral foregut endoderm (Shiojiri, 1997; Zaret and Grompe, 2008; Tremblay and Zaret, 2005). However, the cell-intrinsic factors responsible for IHBD and EHBD system specification are unclear. Recently, Spence et al. (2009) by using a PDX1-Cre transgenic mouse showed that hepatocytes and IHBD cells descend from Pdx1− cells while the EHBD cells including the ventral pancreas derive from Pdx1+ cells. These data were corroborated by a study in our lab, where we found that adult mouse gallbladder stem cells have a distinct phenotypic and expression profile compared to adult mouse IHBD cells (Manohar et al., 2011). However, the differences between human IHBD and EHBD cells have not yet been explored.