DOI 1.17/s1215-12-949- Scope nd Impct of Interntionl Reserch in Humn Pluripotent Stem Cells Peter Löser & Sine Koold & Anke Guhr & Frnz-Josef Müller & Andres Kurtz # The Author(s) 212. This rticle is pulished with open ccess t Springerlink.com Astrct In recent study pulished in this journl it ws climed tht the rte of pulictions from -sed uthors in the humn emryonic stem cell (hesc) reserch field ws slowing or even declining from 28 to 21. It ws ssumed tht this is the result of long-term effects of the Bush dministrtion s funding policy for hesc reserch nd the uncertin policy environment of recent yers. In the present study, we nlyzed pool of more thn 1,7 originl hesc reserch ppers pulished world-wide from 27 to 211. In contrst to the previous study, our results do not support the hypothesis of decline in the productivity of -sed reserch ut rther confirm nerly unchnged leding position of reserch in the hesc field with respect to oth puliction numers nd impct of reserch. Moreover, we nlyzed out 5 ppers reporting originl reserch Electronic supplementry mteril The online version of this rticle (doi:1.17/s1215-12-949-) contins supplementry mteril, which is ville to uthorized users. P. Löser (*) : S. Koold : A. Guhr Roert Koch Institute, DGZ-Ring 1, 1386 Berlin, Germny e-mil: loeserp@rki.de F.-J. Müller Zentrum für Integrtive Psychitrie, Kiel, Germny F.-J. Müller Schmerzklinik Kiel, Kiel, Germny A. Kurtz Berlin Brndenurg Center for Regenertive Therpies, Berlin, Germny A. Kurtz Seoul Ntionl University, Seoul, Kore involving humn induced pluripotent stem cells (hipscs) pulished through 211 nd found dominnt position of reserch in this reserch field s well. Keywords Humn emryonic stem cells (hesc). Humn induced pluripotent stem cells (hipsc). Puliction numers. Impct fctors. Cittion frequencies Introduction The question how the effects of the federl funding policy for humn emryonic stem cell (hesc) reserch cn e mesured is mtter of dete. Wheres some hve vlued puliction numers s evidence for growing underperformnce of the United Sttes in this reserch field [1, 2], we oserved n unltered high level of contriution of the United Sttes to hesc reserch over the lst decde [3, 4]. In ddition, severl studies climed tht the Bush dministrtion s funding policy ws custive for the preferentil use of only few hesc lines, nmely Wicell s H1 nd H9 lines [5 7], while we hve shown tht the preferentil use of certin hesc lines is independent of ntion sstemcell policy [4]. Rther, we found tht the current glol stem cell usge ptterns cn e effortlessly explined y cumultive dvntge process independent of restrictive or permissive policy influence, nd we showed tht this model nerly perfectly mirrors fctul worldwide stem cell usge ptterns [8]. In recent pper pulished in this journl nd entitled The Rce Is On: Humn Emryonic Stem Cell Reserch Goes Glol, regionl differences in hesc linege use nd decrese in studies from -sed reserch groups were reported for period spnning from 28 to 21 [9]. Inter li it ws ssumed tht lingering effects of the prohiitive stem cell funding policies etween 21 nd 28 nd n uncertin policy environment of the first hlf of the Om
dministrtion ws responsile for n oserved decrese in productivity of -sed groups in this field. It ws stted tht more ntions joined the hesc rce in this period of time y ggressively pulishing in the peer-reviewed literture. Aprt from the prolem tht counting ppers pulished until 21 might e not suitle mesure for possile effects of the ltered stem cell funding policy estlished in the second hlf of 29, we hve dditionl douts on the conclusions drwn in this study. While the differences in the regionl usge of hesc lines oserved y DeRouen nd co-workers were lredy reported efore [4], our nlysis of comprehensive dtset on originl hesc literture pulished from 27 to 211 shows differentsitutionfor-sedhescreserchthnreportedinthe study y DeRouen nd co-workers. Our investigtion of hesc reserch ppers revels tht oth the shre in totl numers of pulictions produced worldwide nd the impct of ppers originting from -sed reserch groups remined nerly unltered over the lst yers. In ddition, our nlysis of humn induced pluripotent stem cell (hipsc) reserch pulished through 211 indictes moderte decline in the dominnce in this politiclly non-regulted reserch field ut nevertheless confirms the strong nd leding position of -sed hipsc reserch. Methods Dt Repositories nd Puliction Selection The nlyses re sed on two literture dt nks hrouring 2,47 originl reserch studies involving experimentl use of hescs pulished from 1998 to 211 nd 514 originl hipsc reserch ppers pulished from 27 to 211, respectively. The dt nk on hesc studies ws estlished in 25 ccording to the methods reported erlier [1] nd lso contins informtion on nerly 1,6 hesc lines nd their usge in reserch sed on pulished dt. The hipsc pper repository ws set up in 29 ccording to the principles reported recently [11]. Both dtsets re updted on n nnul sis y mnul inspection of lrge pper pools resulting from the respective serches of the PuMed dtse ccessile through the NIH Ntionl Lirry of Medicine (NIH/NLM). It should e noted, tht oth repositories only contin studies tht report on originl experimentl work on humn pluripotent stem cells. Reviews, Comments, Editorils s well s work on ethicl nd politicl spects of reserch in humn pluripotent stem cells re not included. We lso did not consider studies, in which only mteril or cells derived from hescs or hipscs (such s RNA from hescs or crdiomyocytes derived from hipscs) were used or in which dt otined in previous studies (e. g. gene expression dt ville from the GEO dtse) were nlysed. Pulictions of protocols tht summrize previously reported experimentl work were lso excluded from our dtsets. Assignment of ppers to countries ws ccording to the institutionl ffilition of the corresponding uthor. From 27 to 211, 1934 studies involving use of hescs nd 512 hipsc reserch ppers in line with the outlined criteri were pulished, respectively. Ppers pre-pulished in 211 ut printed only in 212 were not included in the nlysis. In portion of these studies oth hescs nd hipscs were used resulting in n intersection of 392 ppers which re present in oth dtsets. In 174 of those ppers hescs nd hipscs re either investigted in prllel e. g. to drive conclusions on roder pnel of humn pluripotent stem cells [4, 12], or hipscs were used to confirm results otined with hescs in the sme study. However, in the remining 218 of these studies hescs were only used for mere comprison with hipscs e. g. to verify pluripotency of novel hipsc lines. These 218 ppers were excluded from the nlysis of hesc studies giving rise to pool of 1,716 hesc reserch ppers pulished from 27 to 211 tht were nlysed in the present study. In cse of hipsc reserch ctivities, nlysis ws strted in 28 so tht pioneering work on hipscs [13, 14] ws omitted. The complete pper list is ville on request. Determintion of Averge Impct Fctors The determintion of impct fctors ws performed using the Five Yer Impct Fctors for 21 pulished in the Journl Cittion Reports [15]. Of 361 journls tht pulished experimentl work on hescs, 33 did not hve n Impct Fctor, ffecting 45 ppers. In cse of hipsc studies, 1 of 123 journls tht pulished experimentl work did not hve n Impct Fctor ffecting 12 studies. These 45 nd 12 ppers, respectively, were not included in the nlyses. Consequently, 1,671 hesc nd 5 hipsc studies were nlysed for Journl Impct Fctors. The Five Yer Impct Fctor for ech journl tht hd pulished experimentl hesc or hipsc work, respectively, ws multiplied y the numer of ppers tht were pulished in this journl. The results were dded nd divided y the totl pper numers to otin the verge Five Yer Impct Fctors. Determintion of Averge Cittion Frequencies 1,289 hesc ppers pulished from 27 to 21 nd 267 hipsc reserch ppers pulished from 28 to 21 were nlysed for their overll cittion frequencies y the end of 211 using the Scopus dtse (http://www.scopus.com/ home.url). For 4 hesc nd 2 hipsc ppers, respectively, no cittion frequency could e determined since the journls re not listed in the Scopus dtse. These ppers were omitted from the nlysis. Averge nnul cittion
frequencies were determined y dividing the cittion numer y the numer of yers fter the study ws pulished (e. g. for study tht ws pulished in 27, numer of cittions from 28 to 211 ws summted nd divided y 4). Cittions in the yer of puliction of pper (in print) were not considered. Cittion nlysis ws performed in July 212. Results Numer of hesc Studies Shre in worldwide hesc studies (%) 5 45 4 35 3 25 2 15 1 5 7 6 5 4 3 2 1 totl 27 28 29 21 211 27 28 29 21 211 Fig. 1 hesc reserch ppers from 27 to 211. Shown re the solute numer of hesc reserch ppers () nd the reltive shre of nd -sed studies in the totl numer of hesc ppers () Figure 1 shows the results of our nlyses of those 1,716 reserch ppers tht involved experimentl use of hescs nd tht where pulished etween 27 nd 211 in English lnguge journls listed in the Pu Med dt se (for detils see suppl. Tle 1). Studies in which hescs were used merely for comprison with other humn pluripotent stem cells such s hipscs were not considered. The numer of ppers from -sed nd groups mrkedly incresed from 27 to 211 (Fig. 1). We oserved slight slowdown in the increse of pper numers from 29 to 211, which might e due to shift of the scientific interest to hipscs in the yers fter 27. However, the shre in overll pulictions in hesc remined reltively constnt etween - nd non- sed groups with moderte outlier in 29 (Fig. 1). The 714 ppers pulished y -sed groups in this fiveyer period ccount for out 41.6 % of hesc work pulished world-wide. This vlue is nerly identicl to tht from the previous five-yer period (22 to 26) when the shre of -sed work ws 41.2 % (185 of 449 hesc reserch ppers). Thus, our dt do not revel ny decline in the contriution of -sed reserch groups to the reltive numer of hesc pulictions. Rther they confirm tht the output of reserch in hescs hs incresed oth in nd outside the United Sttes to nerly indistinguishle degree. We lso investigted in detil the contriution of groups sed in countries with t lest 3 reserch ppers in the hesc field from 27 to 211 (suppl. Figure 1). Although there ws tendency towrds n increse in the numer of hesc reserch studies in most countries from 27 to 211, we did not oserve n overll reltive increse in the percent shre of studies from these countries in worldwide puliction numers. For exmple, wheres the reltive shre of studies from Jpnese groups remined nerly constnt, it incresed mrkedly for ppers from Chin nd rther decresed for studies from Isrel or Singpore in this period of time. It should e noted tht in some countries with rther permissive stem cell policy (such s Isrel or Singpore) the solute reserch output remined nerly unchnged over the pst 5 yers. On the other hnd, we oserved n increse in the numer of pulished studies from Germny which hs one of the most restrictive stem cell policies world-wide. In generl, the numer of countries which re home to reserch groups pulishing results of experimentl work involving hescs incresed from 23 in the period 22 to 26 to 35 in the 27 to 211 period. Although dt on puliction numers my provide some insight in pst reserch ctivities, they do not give strong indiction on the ctul impct of this work on interntionl reserch. We therefore investigted the verge Impct Fctor of journls tht pulished hesc work from 27 to 211 s further possile proxy for the potentil cdemic impct of ntion s sic nd preclinicl hesc reserch. Figure 2 shows the result of the nlysis of those 1,671 hesc reserch ppers tht were pulished from 27 to 211 in journls which hve n Impct Fctor ccording to the Journl Impct Fctors list for 21. The weighted verge Five Yer Impct Fctor of journls tht pulished hesc work from 27 to 211 ws out 7.5. However, hesc reserch studies from groups sed in certin countries such s Cnd, Frnce nd the United Sttes were pulished in journls with n higher verge Five Yer Impct Fctor (9.94, 9.62 nd 9.38, respectively) while ppers from groups sed in Chin, Kore or Austrli tended to pper in less influentil journls (verge Five Yer Impct Fctor 4.23, 4.8 nd 5.57, respectively). In the 5 yer period nlyzed, moderte decrese in the verge Impct Fctor of Journls pulishing studies from groups ws oserved, while studies from the United Sttes were pulished in journls
Cnd Frnce United Sttes Isrel Germny United Kingdom Singpore Jpn Spin Sweden Austrli Kore Chin others worldwide 7.11 7.9 6.93 6.53 6.38 5.85 5.82 5.57 4.8 4.23 5.14 7.5 9.94 9.62 9.38 2 4 6 8 1 12 Five Yer Journls Impct Fctor Averge Five Yer Impct Fctor 12 1 8 6 4 2 totl 27 28 29 21 211 Yer Fig. 2 Impct of Journls tht pulished hesc reserch ppers from 27 to 211. Overll verge Five Yer Impct Fctors 21 for hesc reserch ppers pulished from 27 to 211. Dt for those 13 countries tht contriuted more thn 3 studies to the hesc reserch field in this period re shown individully, dt for the remining 22 ntions tht contriuted to hesc reserch re merged in others. Averge Five Yer Impct Fctors 21 for hesc reserch ppers from nd -sed groups for individul yers with n nerly constnt verge Impct Fctor (Fig. 2) underlining the nerly unltered high visiility of hesc studies from the United Sttes. However, the Impct Fctor of journl does not necessrily reflect the ctul influence of ech individul study pulished in this journl. Using the Scopus dt se, we therefore nlyzed the fctul cittion numers until 211 of hesc reserch ppers pulished from 27 to the end of 21. The high impct of journls pulishing -sed hesc reserch is lso reflected in the cittion numers. hesc reserch ppers pulished from 27 to 21 were cited t n verge frequency of 9.5 per yer. However, studies from the United Sttes were cited t n verge of 12.6 times yer, while ppers from other countries were Fig. 3 Averge nnul cittion frequencies for hesc reserch ppers pulished from 27 to 21. Cittion nlysis ws performed for the yers 28 to 211 strting in the yer following the puliction of pper. Averge nnul cittion frequencies from 28 to 211. Temporl course of verge cittion frequencies for the yers indicted. c Shre of ppers within the indicted rnge of cittions per yer in the totl numer of studies from the given countries. Ppers were grouped ccording to their verge nnul cittion frequency from 28 to 211 worldwide United Sttes Cnd Germny United Kingdom c Frnce Jpn Isrel Singpore Shre of ppers (%) with verge yerly cittions Spin Sweden Kore Chin Austrli other 1 9 8 7 6 5 4 3 2 1 9.5 12.6 11.4 1.1 9.6 9.3 8.7 8. 7.6 6.3 5.8 5.1 4.9 4.2 6.5 2 4 6 8 1 12 14 Averge numer of cittions per study nd yer Averge numer of cittions per study nd yer 18 16 14 12 1 8 6 4 2 totl 27 28 29 21 Yer Averge cittions per study nd yer less thn 1 1 to 2 2 to 3 3 nd more
cited less frequently (Fig. 3). Of note, there is only limited correltion etween the verge Five Yer Impct Fctors of journls tht pulished hesc work nd the verge cittion frequencies. In ddition to ppers from sed groups, only studies from Cnd, Germny nd the United Kingdom were cited more frequently thn the worldwide verge. Moreover, when verge cittion frequencies were investigted on n nnul sis, n only moderte decline ws oserved for studies pulished y groups from 27 to 21. In shrp contrst, verge cittion frequencies of studies from other countries declined y more thn 5 % from 27 to 21 (Fig. 3). To exclude tht the oserveddiversityincittionfrequenciesmongppers from severl ntions is due to extremely frequent cittion of only few populr studies we grouped hesc reserch ppers ccording to their verge cittion frequency per yer (Fig. 3c). The shre of ppers cited less thn 1 times per yer ws 77. % for ppers pulished y groups from 27 to 21, nd the proportion of ppers cited more thn 3 times per yer ws only 2.5 %. In cse of ppers from groups sed in the United Sttes, the shre of rrely cited ppers ws 64.2 %, nd ppers with n nnul cittion frequency of 3 or more ccounted for 8.7 % of ll studies. Therefore, rther rod rnge of hesc ppers contriuted to the high cittion frequency of -sed work. Tken together, our dt confirm reltively constnt ledership of reserch in the hesc field nd strongly rgue ginst the purported decline in the productivity of sed groups in the cdemic ren. Next, we were interested whether similr or different trends cn e oserved in the nerly un-regulted field of hipsc reserch. We nlyzed pulictions on originl work involving hipscs tht ppered in the pst 4 yers (28 to 211, Fig. 4). By the end of 211, t lest 512 ppers descriing experimentl work involving hipscs were ville for this period from English lnguge journls indexed in the PuMed dt se (for detils see suppl. Tle 2). A shrp increse in puliction numers ws oserved from 28 to 211, nd oth - nd -sed groups mrkedly contriuted to the elevted reserch output (Fig. 4). However, we detected moderte decrese in the reltive shre of studies from -sed groups in worldwide puliction numers from 66.7 % in 28 to 48.6 % in 211 (Fig. 4). This might e explined y the erly puliction of pioneering hipsc work y severl -sed groups which cused high populrity of this type of reserch in the following yers ll over the world. It should e noted tht certin countries tht significntly contriuted to hesc reserch in the lst decde such s Sweden, Singpore, Isrel or Kore did not ply mjor role in hipsc reserch y the end of 211. Finlly, we performed n nlysis of Journl Impct Fctors nd cittion frequencies of hipsc reserch ppers Numer of hipsc studies Shre in worldwide hipsc studies (%) 3 25 2 15 1 5 7 6 5 4 3 2 1 28 29 21 211 28 29 21 211 (Fig. 5). Dt for six countries which contriuted t lest 15 originl ppers to the hipsc reserch field from 27 to 211 re shown. Only ppers from groups sed in Spin were pulished in journls with slightly higher verge impct fctor thn studies (Fig. 5), while ppers pulished y groups from the United Sttes from 28 to 21 were cited most frequently (Fig. 5). We oserved good generl correltion etween the verge Five Yer Impct Fctors nd the ctul cittion frequencies. Surprisingly, studies from Jpn which is elieved to hve leding position in the hipsc reserch field seem to e less influentil ccording to oth Journl Impct Fctors nd ctul cittion frequency, despite the high numer of Jpnese ppers in this field. Agin, grouping of ppers ccording to their cittion frequency per yer reveled, tht mjor proportion of studies from the United Sttes were cited more thn 5 times per yer. Thus, rther rod pnel of ppers from groups contriuted to the oserved high cittion rtes. In contrst, only few studies from Jpn or Chin re cited s frequently. Thus, lthough there is totl Fig. 4 hipsc reserch ppers from 27 to 211. Shown re the solute numer of hipsc reserch ppers () nd the reltive shre of nd -sed studies in the totl numer of totl hipsc ppers ()
Spin 15.24 United Sttes 39.8 United Sttes 14.7 Spin 38.3 United Kingdom 12.81 United Kingdom 34.9 Germny 11.69 Germny 27.5 Jpn 8.77 Jpn 18.9 Chin 7.75 Chin 16. other 9.48 others 16.9 worldwide 12.32 worldwide 31.2 5 1 15 2 1 2 3 4 Averge Five Yer Journl Impct Fctor Averge numer of cittions per study nd yer c 6 Shre of ppers (%) with indicted cittion numer 5 4 3 2 1 Averge cittions per study nd yer < 1 1 to 2 2 to 5 > 5 Chin Germny Jpn Spin United Kingdom United Sttes other worldwide Fig. 5 Impct of pulished hipsc reserch. Overll verge Five Yer Impct Fctors 21 for hipsc reserch ppers pulished from 28 to 211. Dt for those 6 countries tht contriuted more thn 15 studies to the hipsc reserch field in this period re shown individully, dt for the remining 14 ntions tht contriuted to hipsc reserch re merged in other. Averge nnul cittion frequencies for hipsc reserch ppers pulished from 28 to 21. Cittion nlysis ws performed for the yers 29 to 211 strting in the yer following the puliction of pper. c Shre of hipsc reserch ppers within the indicted rnge of cittions per yer in the totl numer of studies from the given countries. Ppers were grouped ccording to their verge nnul cittion frequency from 29 to 211 reltive decline in output from -sed groups, sed reserch continues to occupy leding position in the hipsc field s well. Discussion There hs een some controversy on the effects of regultory policies on hesc reserch output nd out the resons for the preferred usge of n only restricted set of hesc lines [2 4, 6, 7, 1, 12]. Most recently, it hs een suggested tht emrgo effects from pst restrictive policies in the my contriute to reduced output y -sed reserchers in recent yers, while ls thrive ecuse they were le to freely use ny hesc cell line without udget restrictions [9]. Our nlysis of the ville dt did not confirm reduced reltive cdemic output or impct of -sed hesc reserch over time. In fct, our dt show tht the numer of pulictions in the hesc reserch field incresed glolly over the pst 5 yers, independent of more or less restrictive stem cell policy or ideology-driven reserch funding. Although short-term effect of restrictive udget policy might hve delyed reserch output in the fter 21 [16], fctors such s generl reserch nd lterntive udgets, reserch cpcities nd humn resources or the vilility of reserch mteril ll contriute to the reserch output nd my compenste for politiclly motivted restrictions. For exmple, in the United Sttes the stte funding for stem cell reserch prtilly exceeded federl funding y the NIH in the lst yers [17]. For the, our dt show no decline in reltive contriution to interntionl hesc reserch s mesured in numers of pulished reserch nd in terms of its impct, nd if nything we found trend towrds reltive increse in the numer of cittions of work pulished y -sed reserchers s compred to work from reserchers
sed outside the United Sttes. Independent of the sitution with 14 hesc reserch ppers pulished in 23 (45.2 % of glol output), 41 in 24 (41.8 %), 49 in 25 (37.1 %) nd 174 in 211 (4.7 %), hesc reserch output incresed glolly with higher numers of pulictions, from 31 in 23 up to newly 43 in 211. The reson for the supposed loss of ledership of the United Sttes in hesc reserch or, more generlly, pluripotent stem cell reserch ws lmed on the restrictive funding policy in the, nd its long-term ftereffects. Alredy in 26 it ws reported tht the shre in hesc studies pulished through 24 experienced decline strting in 21 [1]. Levine identified the United Sttes s n underperformer in hesc reserch reltive to the unrelted RNAi reserch field [2] lthough the conclusions of this study hve een chllenged [3]. A recent cittion nlysis identified lg in production in hesc reserch of up to 4 % ehind nticipted levels when using studies involving RNAi s reference [16]. However, this lg ws most prominent from 21 to 23 nd lthough RNAi ws s hescs first descried in 1998 y -sed group, studies involving RNAi might not e the est choice for the intended comprison. In contrst to pluripotent stem cells, experimentl use of RNAi does neither require rre nd difficult to propgte mteril (such s stem cells in complex culture systems) nor scientists trined in specil experimentl skills eyond common moleculr iology techniques. In our hnds-on experience [18, 19], oth fctors limited significntly the development of the hesc reserch field. There is no dout tht restrictions nd regultory uncertinty cn hve mjor impct on reserchers [2] nd my dely or even prevent scientific progress. However, our nlysis of pulictions does not confirm ut clerly refutes the hypothesis of reltive decline of productivity in hesc reserch. It cn only e speculted out the resons for the pprent discrepncy etween our dt nd the recent findings of DeRouen nd co-workers. While these uthors used dt pool of 2,86 hesc nd hipsc ppers pulished from 1998 to 21 for their nlysis, our dtset for this period of time contins 194 originl reserch ppers. Thus, the pper pool seems to e of comprle size, nd inclusion nd exclusion criteri my e the prime reson for different results otined in oth studies. The pulic vilility of the dtsets used in the pper of DeRouen et l. s well s in other studies from the sme group would hve een helpful for understnding ovious discrepncies. In ddition, the period of time nlyzed y DeRouen nd co-workers did only spn 3 yers nd might not e sufficient to drw pproprite conclusions on the principl development of reserch field. Moreover, it my e questionle in generl whether the numer of pulictions lone is suitle mesure for the impct of ntion s reserch. We suggest tht tking dditionl fctors such s Journl Impct Fctors nd cittion numers into ccount my e more dequte. Doing so, we did not find ny evidence for decline in the contriution to the hesc field. For the essentilly unrestricted reserch on hipsc we found different outcome with respect to the reltive weight of nd glol reserch output. By 28, nerly 7 % of ll hipsc work ws pulished y -sed groups, ut the shre in pulished work on hipscs dropped to elow 5 % in 211. At the sme time, -sed reserch in the hipsc field mintined continuing high visiility. It would e premture to conclude tht the oserved decline in the reltive shre of contriution to the hipsc field my reflect diminished competitiveness of reserch. Rther, we suggest tht the undisputle initil dominnce of reserch in this field ws due to pioneering work of severl -sed groups which cused high populrity of hipsc reserch in the following yers. A reson for the comprtively fst scent of hipsc reserch outside of the might e tht high numer of reserchers hve een trined y now nd re cple to work with humn pluripotent stem cells. The esier vilility of other resources tht re needed for this type of reserch which were uilt up during the previous hesc er my lso contriute to the rpid development of the hipsc field. It is surprising, however, tht reserch from Jpn performed elow verge in terms of impct during the reported time frme. In summry, our dt shows n unltered strong contriution of reserch to the hesc field. This my e supportive for the hypothesis tht reserch output is oviously not severely hmpered y udgetry regultion s long s lterntive udget options re ville [16]. Moreover, reserch on hipscs is chrcterized y moderte decrese in dominnce in this field with regrd to pper numers, while the impct of reserch remins t high level. Fctors such s incresing interntionl collortion, puliction is or distriution of resources my hve specific effects on this type of reserch nd require further investigtion. Conflicts of interest interest. The uthors declre no potentil conflicts of Open Access This rticle is distriuted under the terms of the Cretive Commons Attriution License which permits ny use, distriution, nd reproduction in ny medium, provided the originl uthor(s) nd the source re credited. References 1. Owen-Smith, J., & McCormick, J. (26). An interntionl gp in humn ES cell reserch. Nture Biotechnology, 24, 391 392. 2. Levine, A. D. (28). Identifying under- nd overperforming countries in reserch relted to humn emryonic stem cells. Cell Stem Cell, 2, 521 524.
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