Creating Patient-Specific Neural Cells for the in Vitro Study of Brain Disorders

Kristen J. Brennand; M. Carol Marchetto; Nissim Benvenisty; Oliver Brüstle; Allison Ebert; Juan Carlos Izpisua Belmonte; Ajamete Kaykas; Madeline A. Lancaster; Frederick J. Livesey; Michael J. McConnell; Ronald D. McKay; Eric M. Morrow; Alysson R. Muotri; David M. Panchision; Lee L. Rubin; Akira Sawa; Frank Soldner; Hongjun Song; Lorenz Studer; Sally Temple; Flora M. Vaccarino; Jun Wu; Pierre Vanderhaeghen; Fred H. Gage; Rudolf Jaenisch

doi:10.1016/j.stemcr.2015.10.011

Creating Patient-Specific Neural Cells for the in Vitro Study of Brain Disorders

Kristen J. Brennand, M. Carol Marchetto, Nissim Benvenisty, Oliver Brüstle, Allison Ebert, Juan Carlos Izpisua Belmonte, Ajamete Kaykas, Madeline A. Lancaster, Frederick J. Livesey, Michael J. McConnell, Ronald D. McKay, Eric M. Morrow, Alysson R. Muotri, David M. Panchision, Lee L. Rubin, Akira Sawa, Frank Soldner, Hongjun Song, Lorenz Studer, Sally TempleFlora M. Vaccarino, Jun Wu, Pierre Vanderhaeghen, Fred H. Gage^*, Rudolf Jaenisch

^*Corresponding author for this work

Department of Genetics

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

Abstract

As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

Original language	American English
Pages (from-to)	933-945
Number of pages	13
Journal	Stem Cell Reports
Volume	5
Issue number	6
DOIs	https://doi.org/10.1016/j.stemcr.2015.10.011
State	Published - 8 Dec 2015

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health through grants R01MH101454 (K.J.B.), R01MH095741 (F.H.G.), U01MH1068821 (F.H.G.), R01NS088538 (R.J.), 2R01MH104610 (R.J.), R01MH102418 (E.M.M.), R01MH105442 (E.M.M.), R01MH094753 (A.R.M.), R01MH103134 (A.R.M.), P01NS066888 (L.L.R.), P50MH094268 (A.S.), R01MH092443 (A.S.), R01MH105660 (A.S.), R33MH087874 (H.S.), U19MH107367 (A.R.M.), R01NS047344 (H.S.), RF1AG042932 (S.T.), R01MH089176 (F.M.V.), and R21MH087879 (F.M.V.); the Department of Defense through award W81XWH-13-1-0414 (F.H.G., M.J.M.); the California Institute for Regenerative Medicine (CIRM) through grant TR4-06747 (A.R.M.); the State of Connecticut (F.M.V.); Maryland Stem Cell Research Fund (H.S.); the Medical Research Council through grant MC_UP_1201/9 (M.A.L.); The Wellcome Trust (Investigator Award to F.J.L.); EU 7th Framework Programme NeuroStemCellRepair through grant 602278 (O.B.); the German Federal Ministry of Education and Research through grants 1615608A (Neuroallianz) (O.B.) and 01ZX1314A (IntegraMent) (O.B.); the North Rhine Westphalian Ministry of Innovation through grant 1403ts007e (StemCellFactory; http://www.stemcellfactory.de ) (O.B.); the Belgian FNRS (P.V.); FMRE (P.V.), IUAP (P.V.); WELBIO (P.V.); the ERC (P.V.); the Universidad Católica San Antonio de Murcia (J.C.I.B.); the Brain and Behavior Research Foundation (K.J.B., A.S., A.R.M., F.M.V.); Stanley Foundation (A.S.); the Simons Foundation (F.M.V.); the New York Stem Cell Foundation (K.J.B.); the Harvard Stem Cell Institute (L.L.R.); the Azrieli Foundation (N.B.); SMA Foundation (L.L.R.); S-R/RUSK (A.S.); Regenerative Research Foundation (S.T.); the G. Harold and Leila Y. Mathers Charitable Foundation (J.C.I.B., F.H.G.); The Leona M. and Harry B. Helmsley Charitable Trust (J.C.I.B., F.H.G.); the Engman Foundation (F.H.G.); the JPB Foundation (F.H.G.); Annette C. Merle-Smith (F.H.G.); JPB Foundation (F.H.G.); and Takeda Pharmaceutical International (F.H.G.).

Publisher Copyright:
© 2015 The Authors.

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Brennand, K. J., Marchetto, M. C., Benvenisty, N., Brüstle, O., Ebert, A., Izpisua Belmonte, J. C., Kaykas, A., Lancaster, M. A., Livesey, F. J., McConnell, M. J., McKay, R. D., Morrow, E. M., Muotri, A. R., Panchision, D. M., Rubin, L. L., Sawa, A., Soldner, F., Song, H., Studer, L., ... Jaenisch, R. (2015). Creating Patient-Specific Neural Cells for the in Vitro Study of Brain Disorders. Stem Cell Reports, 5(6), 933-945. https://doi.org/10.1016/j.stemcr.2015.10.011

@article{e9c8eeaa22ff407bb2be21e66681ec29,

title = "Creating Patient-Specific Neural Cells for the in Vitro Study of Brain Disorders",

abstract = "As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.",

author = "Brennand, {Kristen J.} and Marchetto, {M. Carol} and Nissim Benvenisty and Oliver Br{\"u}stle and Allison Ebert and {Izpisua Belmonte}, {Juan Carlos} and Ajamete Kaykas and Lancaster, {Madeline A.} and Livesey, {Frederick J.} and McConnell, {Michael J.} and McKay, {Ronald D.} and Morrow, {Eric M.} and Muotri, {Alysson R.} and Panchision, {David M.} and Rubin, {Lee L.} and Akira Sawa and Frank Soldner and Hongjun Song and Lorenz Studer and Sally Temple and Vaccarino, {Flora M.} and Jun Wu and Pierre Vanderhaeghen and Gage, {Fred H.} and Rudolf Jaenisch",

note = "Funding Information: This work was supported by the National Institutes of Health through grants R01MH101454 (K.J.B.), R01MH095741 (F.H.G.), U01MH1068821 (F.H.G.), R01NS088538 (R.J.), 2R01MH104610 (R.J.), R01MH102418 (E.M.M.), R01MH105442 (E.M.M.), R01MH094753 (A.R.M.), R01MH103134 (A.R.M.), P01NS066888 (L.L.R.), P50MH094268 (A.S.), R01MH092443 (A.S.), R01MH105660 (A.S.), R33MH087874 (H.S.), U19MH107367 (A.R.M.), R01NS047344 (H.S.), RF1AG042932 (S.T.), R01MH089176 (F.M.V.), and R21MH087879 (F.M.V.); the Department of Defense through award W81XWH-13-1-0414 (F.H.G., M.J.M.); the California Institute for Regenerative Medicine (CIRM) through grant TR4-06747 (A.R.M.); the State of Connecticut (F.M.V.); Maryland Stem Cell Research Fund (H.S.); the Medical Research Council through grant MC_UP_1201/9 (M.A.L.); The Wellcome Trust (Investigator Award to F.J.L.); EU 7th Framework Programme NeuroStemCellRepair through grant 602278 (O.B.); the German Federal Ministry of Education and Research through grants 1615608A (Neuroallianz) (O.B.) and 01ZX1314A (IntegraMent) (O.B.); the North Rhine Westphalian Ministry of Innovation through grant 1403ts007e (StemCellFactory; http://www.stemcellfactory.de ) (O.B.); the Belgian FNRS (P.V.); FMRE (P.V.), IUAP (P.V.); WELBIO (P.V.); the ERC (P.V.); the Universidad Cat{\'o}lica San Antonio de Murcia (J.C.I.B.); the Brain and Behavior Research Foundation (K.J.B., A.S., A.R.M., F.M.V.); Stanley Foundation (A.S.); the Simons Foundation (F.M.V.); the New York Stem Cell Foundation (K.J.B.); the Harvard Stem Cell Institute (L.L.R.); the Azrieli Foundation (N.B.); SMA Foundation (L.L.R.); S-R/RUSK (A.S.); Regenerative Research Foundation (S.T.); the G. Harold and Leila Y. Mathers Charitable Foundation (J.C.I.B., F.H.G.); The Leona M. and Harry B. Helmsley Charitable Trust (J.C.I.B., F.H.G.); the Engman Foundation (F.H.G.); the JPB Foundation (F.H.G.); Annette C. Merle-Smith (F.H.G.); JPB Foundation (F.H.G.); and Takeda Pharmaceutical International (F.H.G.). Publisher Copyright: {\textcopyright} 2015 The Authors.",

year = "2015",

month = dec,

day = "8",

doi = "10.1016/j.stemcr.2015.10.011",

language = "American English",

volume = "5",

pages = "933--945",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

number = "6",

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Brennand, KJ, Marchetto, MC, Benvenisty, N, Brüstle, O, Ebert, A, Izpisua Belmonte, JC, Kaykas, A, Lancaster, MA, Livesey, FJ, McConnell, MJ, McKay, RD, Morrow, EM, Muotri, AR, Panchision, DM, Rubin, LL, Sawa, A, Soldner, F, Song, H, Studer, L, Temple, S, Vaccarino, FM, Wu, J, Vanderhaeghen, P, Gage, FH & Jaenisch, R 2015, 'Creating Patient-Specific Neural Cells for the in Vitro Study of Brain Disorders', Stem Cell Reports, vol. 5, no. 6, pp. 933-945. https://doi.org/10.1016/j.stemcr.2015.10.011

TY - JOUR

T1 - Creating Patient-Specific Neural Cells for the in Vitro Study of Brain Disorders

AU - Brennand, Kristen J.

AU - Marchetto, M. Carol

AU - Benvenisty, Nissim

AU - Brüstle, Oliver

AU - Ebert, Allison

AU - Izpisua Belmonte, Juan Carlos

AU - Kaykas, Ajamete

AU - Lancaster, Madeline A.

AU - Livesey, Frederick J.

AU - McConnell, Michael J.

AU - McKay, Ronald D.

AU - Morrow, Eric M.

AU - Muotri, Alysson R.

AU - Panchision, David M.

AU - Rubin, Lee L.

AU - Sawa, Akira

AU - Soldner, Frank

AU - Song, Hongjun

AU - Studer, Lorenz

AU - Temple, Sally

AU - Vaccarino, Flora M.

AU - Wu, Jun

AU - Vanderhaeghen, Pierre

AU - Gage, Fred H.

AU - Jaenisch, Rudolf

N1 - Funding Information: This work was supported by the National Institutes of Health through grants R01MH101454 (K.J.B.), R01MH095741 (F.H.G.), U01MH1068821 (F.H.G.), R01NS088538 (R.J.), 2R01MH104610 (R.J.), R01MH102418 (E.M.M.), R01MH105442 (E.M.M.), R01MH094753 (A.R.M.), R01MH103134 (A.R.M.), P01NS066888 (L.L.R.), P50MH094268 (A.S.), R01MH092443 (A.S.), R01MH105660 (A.S.), R33MH087874 (H.S.), U19MH107367 (A.R.M.), R01NS047344 (H.S.), RF1AG042932 (S.T.), R01MH089176 (F.M.V.), and R21MH087879 (F.M.V.); the Department of Defense through award W81XWH-13-1-0414 (F.H.G., M.J.M.); the California Institute for Regenerative Medicine (CIRM) through grant TR4-06747 (A.R.M.); the State of Connecticut (F.M.V.); Maryland Stem Cell Research Fund (H.S.); the Medical Research Council through grant MC_UP_1201/9 (M.A.L.); The Wellcome Trust (Investigator Award to F.J.L.); EU 7th Framework Programme NeuroStemCellRepair through grant 602278 (O.B.); the German Federal Ministry of Education and Research through grants 1615608A (Neuroallianz) (O.B.) and 01ZX1314A (IntegraMent) (O.B.); the North Rhine Westphalian Ministry of Innovation through grant 1403ts007e (StemCellFactory; http://www.stemcellfactory.de ) (O.B.); the Belgian FNRS (P.V.); FMRE (P.V.), IUAP (P.V.); WELBIO (P.V.); the ERC (P.V.); the Universidad Católica San Antonio de Murcia (J.C.I.B.); the Brain and Behavior Research Foundation (K.J.B., A.S., A.R.M., F.M.V.); Stanley Foundation (A.S.); the Simons Foundation (F.M.V.); the New York Stem Cell Foundation (K.J.B.); the Harvard Stem Cell Institute (L.L.R.); the Azrieli Foundation (N.B.); SMA Foundation (L.L.R.); S-R/RUSK (A.S.); Regenerative Research Foundation (S.T.); the G. Harold and Leila Y. Mathers Charitable Foundation (J.C.I.B., F.H.G.); The Leona M. and Harry B. Helmsley Charitable Trust (J.C.I.B., F.H.G.); the Engman Foundation (F.H.G.); the JPB Foundation (F.H.G.); Annette C. Merle-Smith (F.H.G.); JPB Foundation (F.H.G.); and Takeda Pharmaceutical International (F.H.G.). Publisher Copyright: © 2015 The Authors.

PY - 2015/12/8

Y1 - 2015/12/8

N2 - As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

AB - As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

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DO - 10.1016/j.stemcr.2015.10.011

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SP - 933

EP - 945

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 6

ER -

Creating Patient-Specific Neural Cells for the in Vitro Study of Brain Disorders

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