Human embryonic and induced pluripotent stem cell research trends: complementation and diversification of the field

Abstract

Research in human induced pluripotent stem cells (hiPSCs) is rapidly developing and there are expectations that this research may obviate the need to use human embryonic stem cells (hESCs), the ethics of which has been a subject of controversy for more than 15 years. In this study, we investigated approximately 3,400 original research papers that reported an experimental use of these types of human pluripotent stem cells (hPSCs) and were published from 2008 to 2013. We found that research into both cell types was conducted independently and further expanded, accompanied by a growing intersection of both research fields. Moreover, an in-depth analysis of papers that reported the use of both cell types indicates that hESCs are still being used as a "gold standard," but in a declining proportion of publications. Instead, the expanding research field is diversifying and hESC and hiPSC lines are increasingly being used in more independent research and application areas.

Figure 1

Worldwide Research in hESCs (A) Number of hESC research papers published worldwide from 2000 to 2013. Note that research papers in which hESCs were solely used for comparison with hiPSCs (“gold standard”) were not included. (B) Allocation of hESC research papers to individual nations according to the affiliation of the corresponding author. Shown is the share (in percent) of papers from a given nation in relation to the total number of papers for the indicated period. Nations with more than 40 original publications in the hESC field were included.

Figure 2

Worldwide Research in hiPSCs (A) Number of original research papers involving hiPSCs and published worldwide from 2008 to 2013. (B) Allocation of hiPSC research papers to individual nations according to the affiliation of the corresponding author. Shown is the share (in percent) of papers from a given nation in relation to the total number of papers for the indicated period. Nations with more than ten original research papers involving hiPSCs were included.

Figure 3

Impact of Research Papers Involving hPSCs from Selected Countries Average number of citations per paper and year of original research papers involving hESCs (A) or hiPSCs (B). Papers published from 2008 to 2012 by research groups located in the indicated countries were included in the citation analysis. Please note that studies that involved hESCs solely for the purpose of comparison with hiPSCs were not considered.

Figure 4

Use of hPSCs in Experimental Research from 2008 to 2013 (A) Number of original research papers involving hESCs, hiPSCs, or both. (B) Number of original research papers that were published in the indicated years and were based on hESCs only (squares), hiPSCs only (triangles), or both cell types (crosses). The total numbers of research papers on hPSCs are represented by trapezoids. (C) Simultaneous use of hESCs and hiPSCs in experimental research. Shown is the share of studies (in percent) that used hiPSCs and hESCs simultaneously in relation to the total number of hiPSC papers (squares) and hESC papers (triangles) published in the indicated years. Please note that for this analysis, all papers involving hESCs were used.

Figure 5

Type of Use of hESCs in Studies Reporting Experimental Application of Both hiPSCs and hESCs Data are based on analysis of all papers reporting simultaneous experimental use of hESCs and hiPSCs, and published in 2008–2013 (n = 890, 100%). The share (in percent) was determined for papers in which hESCs were solely used for the purpose of comparison with hiPSCs (“gold standard” usage, triangles) or in which hESCs served as an autonomous research object (circles). Please note that the solid line (circles) also indicates studies in which hiPSCs played only a minor role.