International Coordination of Large-Scale Human Induced Pluripotent Stem Cell Initiatives: Wellcome Trust and ISSCR Workshops White Paper

There is growing recognition of the potential value of human induced pluripotent stem cells (hiPSC) for understanding disease and identifying drugs targets. This has been reflected in the establishment of multiple large-scale hiPSC initiatives worldwide. Representatives of these met recently at a workshop supported by the Welcome Trust in the UK and in a focus session at the 2014 ISSCR annual meeting in Vancouver. The purpose was to discuss strategies for making thousands of hiPSC lines widely available with as few restrictions as possible while retaining financial viability and donor privacy. The outcome of these discussions is described here. There is growing recognition of the potential value of human induced pluripotent stem cells (hiPSC) for understanding disease and identifying drugs targets. This has been reflected in the establishment of multiple large-scale hiPSC initiatives worldwide. Representatives of these met recently at a workshop supported by the Welcome Trust in the UK and in a focus session at the 2014 ISSCR annual meeting in Vancouver. The purpose was to discuss strategies for making thousands of hiPSC lines widely available with as few restrictions as possible while retaining financial viability and donor privacy. The outcome of these discussions is described here. Main TextIntroductionThe ability to generate human induced pluripotent stem cells (hiPSCs) by direct reprogramming of somatic cells by simple overexpression of transcription factors initiated a paradigm shift in biomedical science (Takahashi et al., 2007Takahashi K. Tanabe K. Ohnuki M. Narita M. Ichisaka T. Tomoda K. Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors.Cell. 2007; 131: 861-872Abstract Full Text Full Text PDF PubMed Scopus (14654) Google Scholar, Yu et al., 2007Yu J. Vodyanik M.A. Smuga-Otto K. Antosiewicz-Bourget J. Frane J.L. Tian S. Nie J. Jonsdottir G.A. Ruotti V. Stewart R. et al.Induced pluripotent stem cell lines derived from human somatic cells.Science. 2007; 318: 1917-1920Crossref PubMed Scopus (8045) Google Scholar). In just a few years, hiPSCs have opened new fields of investigation not only in cellular reprogramming itself but also in creating human models of inherited diseases for basic research in pathological mechanisms and drug target discovery. The increasing numbers of grant applications and publications that include hiPSCs (>7000 manuscripts have been published since 2007) are evidence of how these cells have captured the imagination of those both inside and outside this rapidly evolving large-scale initiatives have been to this growing and hiPSC for and and understanding the of disease in the of these large-scale initiatives to hiPSC lines from of and in and and the focus in applications in disease and drug these initiatives to to for with few that human disease models for are to include and and that are the are to with to to and of and and of donor hiPSC for for for disease and with lines from and and for research for and hiPSC lines from drug and for fibroblasts and for for research and by and by and for lines from and for disease target drug and pluripotent and of of hiPSC lines of and of the of hiPSC lines for diseases and in a new to of hiPSC lines from disease as as The of these as at the Trust and ISSCR to discuss the and with the of numbers of hiPSC is This the to for and hiPSC and The is that hiPSC lines in the a research of hiPSC the the available for was the to by large-scale hiPSC the of lines the are available to generate hiPSCs from somatic cells and are the transcription factors the in the of target that of the as this a et al., K. R. M. R. R. M. et fibroblasts to induced pluripotent stem PubMed Scopus Google Scholar). reprogramming is widely as that the are and et al., M. M. J. K. pluripotent stem cells PubMed Scopus Google et al., K. M. of human pluripotent stem cells a that not the PubMed Scopus Google et al., J. K. Smuga-Otto K. Tian S. Stewart R. induced pluripotent stem cells of and PubMed Scopus Google to the reprogramming et al., T. et reprogramming to and of human cells with Full Text Full Text PDF PubMed Scopus Google and reprogramming et al., S. R. of human induced pluripotent stem cells by direct of reprogramming Full Text Full Text PDF PubMed Scopus Google Scholar). in and with somatic cell large-scale hiPSC initiatives in of and somatic cell and the hiPSC lines have been widely by research has have reprogramming and the potential for and are and reprogramming is and workshop was that reprogramming are for the with new the factors described by Yamanaka and new as published have been the of cell available from human and to large-scale is was that of by creating a of to and the to the was how cell lines derived and initiatives are lines donor while only to only cell that has the of the of lines and the also has the of of hiPSCs with and for somatic cell to is for large-scale hiPSC of cell from has been to generate and that have and et al., S. T. donor cell human induced pluripotent stem cells to with human stem PubMed Scopus Google Scholar, et al., K. T. K. K. M. M. Tanabe K. Ohnuki M. et in the of induced pluripotent stem cell PubMed Scopus Google Scholar). hiPSCs of the somatic cells from This has been with reprogramming of the of somatic have for the of hiPSCs to as by the in potential of lines derived from adult et al., K. T. K. K. M. M. Tanabe K. Ohnuki M. et in the of induced pluripotent stem cell PubMed Scopus Google Scholar). that in et al., K. M. M. in human induced pluripotent stem cells PubMed Scopus Google Scholar). The in the was that hiPSCs at to the pluripotent and and at was to and was in of the the was that this not hiPSC lines derived from this was as a with a of The for this but to from a of factors et al., in human induced pluripotent stem PubMed Scopus Google and the the of the hiPSC initiatives have to somatic cell of and reprogramming fibroblasts have been the in the and by of the initiatives are from as as and and This is the of a the to reprogramming at a this cell widely by large-scale initiatives are cells from and available as in cell and The of for reprogramming cell is making possible to hiPSC initiatives that as that of the and and the at with of thousands of from that have of cells in are also of increasing are to to generate and hiPSCs defined and not in with cells has been widely to initiatives are and defined as the defined et al., Ruotti V. Smuga-Otto K. et defined for human and PubMed Scopus Google Scholar). The increasing in defined and is by the to and with the the are is not for with The workshop the of identifying the and of and of the stem cell a the of large-scale initiatives hiPSC and of are as to in the of hiPSC initiatives are this for the of hiPSC The has the of hiPSCs by reprogramming in This also and of hiPSCs as as hiPSC are with to and of hiPSCs and of hiPSCs and the for this was as a by the initiatives with the the of these initiatives is to generate of hiPSC lines for a of and the of in of the that for and that of to the pluripotent stem cell that to available to identifying the hiPSC lines a to understanding of the mechanisms and The was to to the pluripotent of hiPSCs in and hiPSCs are by this is by the of the initiatives as the in The evidence is the of with as and by cell transcription was that this to cells as in of et al., R. S. et for in human PubMed Scopus Google the outcome and is that and a to cells and not hiPSC lines of is the and for but as is not and for to generate for thousands of hiPSC lines and There was that and that in to The is this by the outcome of in defined by the of in and a with of hiPSCs in hiPSC lines in of the and by for cell for of the the ability of hiPSCs to cell as the to and was is for hiPSC the cells in include and of as are and and to in numbers of hiPSC of the initiatives to as and the hiPSC lines as basic of the of the the of the in only a of the cell has that in hiPSCs and that of the lines have that at of the in hiPSCs to in of the cells to the as a of the reprogramming the and of these and the was that only to in In are to of thousands of lines and a of the with reprogramming in of hiPSCs of and the is as as the of hiPSC lines with that of pluripotent stem cells The is the only that a of the hiPSC lines This to the of the the for and to how and to generate large-scale of hiPSCs that the to the cells are widely The meeting that include of the as as of cell viability of the of human and at a and is also to cell to potential by hiPSC as have of these for large-scale human initiatives the of cell and and from The of for the and of hiPSC lines a in as and the was that for but that this to has that a of the hiPSC initiatives is to lines that widely the and of the hiPSC lines and the is for these large-scale initiatives to have and for the and to this and and to lines and The of for and of for that disease and to hiPSC lines by a of for disease and drug the of the donor to of value in disease hiPSC lines and available to and This was as to and from for the of hiPSC hiPSC lines a to human and are as the of with diseases and the for in a not possible in and are not This understanding of the of and disease and strategies to and to to have that to of the direct have been as to the to this and and the of the hiPSC lines and to the to in in the of and and evolving for hiPSCs is with of and of have the to lines by and The are by This to for while for In is available from hiPSC lines with this are by a with for a of are and to with the of the The of the to this to by by and to in hiPSCs not only the hiPSC lines but also direct of potential restrictions with the of as and to of the hiPSC the to these that for and in lines in the the ability of to the lines to with to cells from the the that are not by the of hiPSC This is a the a to that the of hiPSCs for drug and cell of the initiatives that of a and for of that not the of the hiPSC in and of in of and of to generate of disease and only in the of are and are by large-scale the Trust is a to generate and hiPSC lines to target The in and in are and to generate a of hiPSC lines with in the was the of and how to with hiPSC lines et al., in human induced pluripotent stem PubMed Scopus Google Scholar). hiPSC lines and for the published in this of hiPSC lines from that widely available as the human stem cell and are widely as and that also to as a to hiPSCs derived from with this the to generate new lines and a of a diseases and disease to disease the of for the stem cell and these are to in with hiPSC from in the the not only the that large-scale hiPSC initiatives are but also the that have the since discovery. from of and to a a of was to the of hiPSC to the of a of hiPSC lines by in the for research in this to for the of new and also for hiPSC lines have to for pluripotent and to cell the and the of these lines with have to and have been initiated the Trust and as the was as a in the There is a of to and this is increasing as the is a for that in and in to with the and by the the to of and from that a to hiPSCs was that of donor and was that this of and and also to with the a as in the of these that both the and and are of and by the initiatives and understanding of the and is the of research and was the that are and The that of defined and that the with the was that cells not by the with of the The of to and a in the in the of large-scale of and in the the initiatives have in this the in both that the of of hiPSCs by the of that the research to and cell lines of This the of lines and the of lines with a disease of and the of the The of reprogramming and for for the that The of for and hiPSC lines in this as et al., J. T. et for and of human and Full Text Full Text PDF PubMed Scopus Google Scholar). The to this at the was the in In available as a this as a to and a The to lines in is to include hiPSC lines are to the hiPSC lines generate to only widely this as a with the of are the and the The hiPSC initiatives to of hiPSC lines from hiPSC initiatives are to generate the of the lines that available in the to these The workshop in and the focus session at the 2014 ISSCR annual meeting the to this and the of and these The of this to for and of hiPSC a of hiPSC lines from the the and and hiPSC lines derived by Main TextIntroductionThe ability to generate human induced pluripotent stem cells (hiPSCs) by direct reprogramming of somatic cells by simple overexpression of transcription factors initiated a paradigm shift in biomedical science (Takahashi et al., 2007Takahashi K. Tanabe K. Ohnuki M. Narita M. Ichisaka T. Tomoda K. Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors.Cell. 2007; 131: 861-872Abstract Full Text Full Text PDF PubMed Scopus (14654) Google Scholar, Yu et al., 2007Yu J. Vodyanik M.A. Smuga-Otto K. Antosiewicz-Bourget J. Frane J.L. Tian S. Nie J. Jonsdottir G.A. Ruotti V. Stewart R. et al.Induced pluripotent stem cell lines derived from human somatic cells.Science. 2007; 318: 1917-1920Crossref PubMed Scopus (8045) Google Scholar). In just a few years, hiPSCs have opened new fields of investigation not only in cellular reprogramming itself but also in creating human models of inherited diseases for basic research in pathological mechanisms and drug target discovery. The increasing numbers of grant applications and publications that include hiPSCs (>7000 manuscripts have been published since 2007) are evidence of how these cells have captured the imagination of those both inside and outside this rapidly evolving large-scale initiatives have been to this growing and hiPSC for and and understanding the of disease in the of these large-scale initiatives to hiPSC lines from of and in and and the focus in applications in disease and drug these initiatives to to for with few that human disease models for are to include and and that are the are to with to to and of and and of donor hiPSC for for for disease and with lines from and and for research for and hiPSC lines from drug and for fibroblasts and for for research and by and by and for lines from and for disease target drug and pluripotent and of of hiPSC lines of and of the of hiPSC lines for diseases and in a new to of hiPSC lines from disease as as The of these as at the Trust and ISSCR to discuss the and with the of numbers of hiPSC is This the to for and hiPSC and The is that hiPSC lines in the a research of hiPSC the the available for was the to by large-scale hiPSC the of lines the are available to generate hiPSCs from somatic cells and are the transcription factors the in the of target that of the as this a et al., K. R. M. R. R. M. et fibroblasts to induced pluripotent stem PubMed Scopus Google Scholar). reprogramming is widely as that the are and et al., M. M. J. K. pluripotent stem cells PubMed Scopus Google et al., K. M. of human pluripotent stem cells a that not the PubMed Scopus Google et al., J. K. Smuga-Otto K. Tian S. Stewart R. induced pluripotent stem cells of and PubMed Scopus Google to the reprogramming et al., T. et reprogramming to and of human cells with Full Text Full Text PDF PubMed Scopus Google and reprogramming et al., S. R. of human induced pluripotent stem cells by direct of reprogramming Full Text Full Text PDF PubMed Scopus Google Scholar). in and with somatic cell large-scale hiPSC initiatives in of and somatic cell and the hiPSC lines have been widely by research has have reprogramming and the potential for and are and reprogramming is and workshop was that reprogramming are for the with new the factors described by Yamanaka and new as published have been the of cell available from human and to large-scale is was that of by creating a of to and the to the was how cell lines derived and initiatives are lines donor while only to only cell that has the of the of lines and the also has the of of hiPSCs with and for somatic cell to is for large-scale hiPSC of cell from has been to generate and that have and et al., S. T. donor cell human induced pluripotent stem cells to with human stem PubMed Scopus Google Scholar, et al., K. T. K. K. M. M. Tanabe K. Ohnuki M. et in the of induced pluripotent stem cell PubMed Scopus Google Scholar). hiPSCs of the somatic cells from This has been with reprogramming of the of somatic have for the of hiPSCs to as by the in potential of lines derived from adult et al., K. T. K. K. M. M. Tanabe K. Ohnuki M. et in the of induced pluripotent stem cell PubMed Scopus Google Scholar). that in et al., K. M. M. in human induced pluripotent stem cells PubMed Scopus Google Scholar). The in the was that hiPSCs at to the pluripotent and and at was to and was in of the the was that this not hiPSC lines derived from this was as a with a of The for this but to from a of factors et al., in human induced pluripotent stem PubMed Scopus Google and the the of the hiPSC initiatives have to somatic cell of and reprogramming fibroblasts have been the in the and by of the initiatives are from as as and and This is the of a the to reprogramming at a this cell widely by large-scale initiatives are cells from and available as in cell and The of for reprogramming cell is making possible to hiPSC initiatives that as that of the and and the at with of thousands of from that have of cells in are also of increasing are to to generate and hiPSCs defined and not in with cells has been widely to initiatives are and defined as the defined et al., Ruotti V. Smuga-Otto K. et defined for human and PubMed Scopus Google Scholar). The increasing in defined and is by the to and with the the are is not for with The workshop the of identifying the and of and of the stem cell a the of large-scale initiatives hiPSC and of are as to in the of hiPSC initiatives are this for the of hiPSC The has the of hiPSCs by reprogramming in This also and of hiPSCs as as hiPSC are with to and of hiPSCs and of hiPSCs and the for this was as a by the initiatives with the the of these initiatives is to generate of hiPSC lines for a of and the of in of the that for and that of to the pluripotent stem cell that to available to identifying the hiPSC lines a to understanding of the mechanisms and The was to to the pluripotent of hiPSCs in and hiPSCs are by this is by the of the initiatives as the in The evidence is the of with as and by cell transcription was that this to cells as in of et al., R. S. et for in human PubMed Scopus Google the outcome and is that and a to cells and not hiPSC lines of is the and for but as is not and for to generate for thousands of hiPSC lines and There was that and that in to The is this by the outcome of in defined by the of in and a with of hiPSCs in hiPSC lines in of the and by for cell for of the the ability of hiPSCs to cell as the to and was is for hiPSC the cells in include and of as are and and to in numbers of hiPSC of the initiatives to as and the hiPSC lines as basic of the of the the of the in only a of the cell has that in hiPSCs and that of the lines have that at of the in hiPSCs to in of the cells to the as a of the reprogramming the and of these and the was that only to in In are to of thousands of lines and a of the with reprogramming in of hiPSCs of and the is as as the of hiPSC lines with that of pluripotent stem cells The is the only that a of the hiPSC lines This to the of the the for and to how and to generate large-scale of hiPSCs that the to the cells are widely The meeting that include of the as as of cell viability of the of human and at a and is also to cell to potential by hiPSC as have of these for large-scale human initiatives the of cell and and from The of for the and of hiPSC lines a in as and the was that for but that this to has that a of the hiPSC initiatives is to lines that widely the and of the hiPSC lines and the is for these large-scale initiatives to have and for the and to this and and to lines and The of for and of for that disease and to hiPSC lines by a of for disease and drug the of the donor to of value in disease hiPSC lines and available to and This was as to and from for the of hiPSC hiPSC lines a to human and are as the of with diseases and the for in a not possible in and are not This understanding of the of and disease and strategies to and to to have that to of the direct have been as to the to this and and the of the hiPSC lines and to the to in in the of and and evolving for hiPSCs is with of and of have the to lines by and The are by This to for while for In is available from hiPSC lines with this are by a with for a of are and to with the of the The of the to this to by by and to in hiPSCs not only the hiPSC lines but also direct of potential restrictions with the of as and to of the hiPSC the to these that for and in lines in the the ability of to the lines to with to cells from the the that are not by the of hiPSC This is a the a to that the of hiPSCs for drug and cell of the initiatives that of a and for of that not the of the hiPSC in and of in of and of to generate of disease and only in the of are and are by large-scale the Trust is a to generate and hiPSC lines to target The in and in are and to generate a of hiPSC lines with in the was the of and how to with hiPSC lines et al., in human induced pluripotent stem PubMed Scopus Google Scholar). hiPSC lines and for the published in this of hiPSC lines from that widely available as the human stem cell and are widely as and that also to as a to hiPSCs derived from with this the to generate new lines and a of a diseases and disease to disease the of for the stem cell and these are to in with hiPSC from in the the not only the that large-scale hiPSC initiatives are but also the that have the since discovery. from of and to a a of was to the of hiPSC to the of a of hiPSC lines by in the for research in this to for the of new and also for hiPSC lines have to for pluripotent and to cell the and the of these lines with have to and have been initiated the Trust and as the was as a in the There is a of to and this is increasing as the is a for that in and in to with the and by the the to of and from that a to hiPSCs was that of donor and was that this of and and also to with the a as in the of these that both the and and are of and by the initiatives and understanding of the and is the of research and was the that are and The that of defined and that the with the was that cells not by the with of the The of to and a in the in the of large-scale of and in the the initiatives have in this the in both that the of of hiPSCs by the of that the research to and cell lines of This the of lines and the of lines with a disease of and the of the The of reprogramming and for for the that The of for and hiPSC lines in this as et al., J. T. et for and of human and Full Text Full Text PDF PubMed Scopus Google Scholar). The to this at the was the in In available as a this as a to and a The to lines in is to include hiPSC lines are to the hiPSC lines generate to only widely this as a with the of are the and the The hiPSC initiatives to of hiPSC lines from hiPSC initiatives are to generate the of the lines that available in the to these The workshop in and the focus session at the 2014 ISSCR annual meeting the to this and the of and these The of this to for and of hiPSC a of hiPSC lines from the the and and hiPSC lines derived by ability to generate human induced pluripotent stem cells (hiPSCs) by direct reprogramming of somatic cells by simple overexpression of transcription factors initiated a paradigm shift in biomedical science (Takahashi et al., 2007Takahashi K. Tanabe K. Ohnuki M. Narita M. Ichisaka T. Tomoda K. Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors.Cell. 2007; 131: 861-872Abstract Full Text Full Text PDF PubMed Scopus (14654) Google Scholar, Yu et al., 2007Yu J. Vodyanik M.A. Smuga-Otto K. Antosiewicz-Bourget J. Frane J.L. Tian S. Nie J. Jonsdottir G.A. Ruotti V. Stewart R. et al.Induced pluripotent stem cell lines derived from human somatic cells.Science. 2007; 318: 1917-1920Crossref PubMed Scopus (8045) Google Scholar). In just a few years, hiPSCs have opened new fields of investigation not only in cellular reprogramming itself but also in creating human models of inherited diseases for basic research in pathological mechanisms and drug target discovery. The increasing numbers of grant applications and publications that include hiPSCs (>7000 manuscripts have been published since 2007) are evidence of how these cells have captured the imagination of those both inside and outside this rapidly evolving large-scale initiatives have been to this growing and hiPSC for and and understanding the of disease in the of these large-scale initiatives to hiPSC lines from of and in and and the focus in applications in disease and drug these initiatives to to for with few that human disease models for are to include and and that are the are to with to to and of and and of donor hiPSC for for for disease and with lines from and and for research for and hiPSC lines from drug and for fibroblasts and for for research and by and by and for lines from and for disease target drug and pluripotent and of of hiPSC lines of and of the of hiPSC lines for diseases and in a new to of hiPSC lines from disease as as The of these as at the Trust and ISSCR to discuss the and with the of numbers of hiPSC is This the to for and hiPSC and The is that hiPSC lines in the a research

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