ABSTRACT Research in human pluripotent stem cells, including human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC), is one of the most dynamic research ﬁelds. Despite the high public attention, especially for hESC research, there is only scattered information on the number of hESC lines and the degree, dynamics, and diversiﬁcation of their use on a global level. In this study we present data on the current number of publicly dis- closed hESC lines, on the extent and impact of experimen- tal work involving hESCs, and on the use of speciﬁc hESC lines in international research. The results are based on the evaluation of nearly 1,000 research papers published by the end of 2008, which describe experimental work on Disclosure of potential conﬂicts of interest is found at the end of this article. INTRODUCTION Research with human embryonic stem cell (hESC) lines has attracted increasing attention over the last decade because these cells have the capability to proliferate indeﬁnitely and to differentiate into any cell type of the body. On the other hand, there has been much controversy about using hESCs due to their origin from early human embryos, which resulted in a wide panel of different national legislations on human ESC research [1]. In a preceding report, we have determined the number of hESC cell lines and quantiﬁed the extent of experimental research involving hESCs [2], but since then hESC research has further intensiﬁed and spread into many more countries. The release of new National Institutes of Health (NIH) guidelines on research involving hESCs in the United States (http://stemcells.nih.gov/policy/2009guideli- nes.htm) has evoked much interest in the question of how many cell lines are available worldwide. However, to date there is no current information on how many hESC lines exist worldwide, and literature data on this question are based on estimates and are somewhat divergent [3, 4]. Although there are now several registries that contain par- EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS Human Embryonic Stem Cell Lines and Their Use in International Research PETER LO¨ SER,a JACQUELINE SCHIRM,a ANKE GUHR,a ANNA M. WOBUS,b ANDREAS KURTZc aRobert Koch Institute, Berlin, Germany; bLeibniz Institute of Plant Genetics and Crop Plant Research, Gatersleben, Germany; cBerlin Brandenburg Center for Regenerative Therapies and European Human Embryonic Stem Cell Registry (hESCreg), Charite´, Berlin, Germany Key Words. Embryonic stem cells • Pluripotent stem cells • hESC Lines • hESC Research • hESC Usage • Human induced pluripotent stem cells • hiPSCs hESCs, and of a comprehensive database of published hESC lines. The average impact of hESC research papers is high at 7.422, with a predominance of research output by the United States. Of at least 1,071 original hESC lines derived up to November 2009 at 87 institutions in 24 coun- tries, only a fraction is thoroughly characterized. Our data show the global predominance of a few hESC lines in research, but also reveal remarkable country-speciﬁc dif- ferences. Comparison of hESC and hiPSC application did not show a diminished role for hESC research, but rather revealed that, up to this time, both ﬁelds continue to expand, exist independently, and partially overlap. STEM CELLS 2010;28:240–246 tially overlapping data sets on a multitude of hESC lines [5– 7], the level of characterization of the cell lines listed in these registries is highly variable and, most importantly, the extent of their use in international research can not be assessed. Moreover, there are no data that elucidate whether there is a preferential use of certain cell lines in different countries. We have determined the number of hESC lines and analyzed the scale of hESC research on a global level, including the use of speciﬁc hESC lines. We found remark- able differences between countries. Our studies are based on the analysis of a databank of hESC lines that was previously described [2, 8] and has been updated regularly up to No- vember 2009, as well as on the evaluation of nearly 1,000 research papers describing experimental work on hESCs up to the end of 2008. MATERIALS AND METHODS The methods for extracting papers on experimental work on hESCs and human induced pluripotent stem cells (hiPSCs) from the PubMed database are given in the supporting information. Author contributions: P.L.: Conception and design, Collection and/or assembly of data, data analysis and interpretation, manuscript writing; J.S.: Collection and/or assembly of data, administrative support; A.G.: Collection and/or assembly of data, administrative support; A.M.W.: Conception and design, data analysis and interpretation, manuscript writing; A.K.: Conception and design, data analysis and interpretation, manuscript writing. Correspondence: Peter Lo¨ser, Ph.D., Robert Koch Institute, DGZ-Ring 1, D-13086 Berlin, Germany. Telephone: þ49-30-18754-3127; Fax: þ49-30-18754-3206; e-mail: loeserp@rki.de Received November 2, 2009; accepted for publication December 11, 2009; ﬁrst pub- lished online in STEM CELLS EXPRESS January 28, 2010. VC AlphaMed Press 1066-5099/2009/$30.00/0 doi: 10.1002/stem.286 STEM CELLS 2010;28:240–246 www.StemCells.com