Where in the World Are the iPS Cells

15 September 2010. Since the discovery, in 2006, that adult cells could be reprogrammed to a pluripotent state, scientists have been excited by the potential of these cells for modeling diseases, screening drugs, and even for cell replacement therapy. The promise of induced pluripotent stem cells (iPSC) led Science magazine to name them as their Breakthrough of the Year in 2008 (see ARF related news story). Among other advantages, these adult-derived stem cells sidestep the ethical issues involved in embryonic stem cell (ESC) research, particularly relevant given renewed legal wrangling over federal funding for ESC experiments (see Dow Jones Newswires story). Nonetheless, scientists must still solve numerous technical challenges before the possibilities of iPS cells can be realized. Two years after Science’s celebration of iPS cells, it seems like an opportune time to survey the state of the field as it affects neurodegenerative disease research. What iPSC lines specific for these diseases are available to researchers now, or will soon become available Who is making them What are some of the technical challenges with these cells

This reporter sought to answer these questions by interviewing 15 scientists in the field. However, this story can’t be comprehensive, and we invite our esteemed readers to fill in any omissions. One thing is clear: Neurodegenerative iPSC lines are mushrooming. Though only a handful of lines have been published to date, a plethora of lines are scheduled to appear in print or be accessible from cell banks within the next few months, for diseases such as Alzheimer’s, Parkinson’s, Huntington’s, ALS, and frontotemporal dementias. Despite the rush to make lines, the field has not yet reached a consensus on the best way to generate these cells, on the best way to differentiate them into mature cell types, or on what is required to validate these cell lines as truly pluripotent and useful. Moreover, iPSC lines harbor tremendous genetic and epigenetic variation, which may pose a problem for comparing data between experiments.

The iPS Cells Are Coming: A Snapshot of Summer 2010

Disease PI Institute Lines Where When
AD John Hardy University College London 1 APP, 1 PS so far Coriell or ECACC 6 mo. – yr.
AD Larry Goldstein UC San Diego Familial and sporadic Larry Goldstein 6 mo. – yr.
AD Asa Abeliovich Columbia Familial and sporadic Asa Abeliovich, Columbia Later

Rudolf Jaenisch M.I.T. Sporadic; familial in development   Now/Later
PD Ole Isacson Harvard/NINDS Consortium 10-15 familial Coriell Early 2011
PD Birgitt Schuele Parkinson’s Institute 15-20 familial and sporadic Parkinson’s Institute Later
PD Helene Plun-Favreau, Patrick Lewis University College London ~12 familial Coriell or ECACC 6 mo. – yr.
PD Asa Abeliovich Columbia Familial and sporadic   Later
PD George Daley Harvard 1 sporadic line HSCI Now
ALS Kevin Eggan Harvard ~12 SOD1 and TDP43 HSCI Weeks
ALS Jeff Rothstein Johns Hopkins/
NINDS Consortium
10-15 familial Coriell Early 2011
HD Leslie Thompson UC-Irvine/
NINDS Consortium
10-15 lines Coriell Early 2011
HD Clive Svendsen Cedars-Sinai Several lines    
HD George Daley Harvard 1 line HSCI Now
FTD John Hardy University College London ~6 tau mutations Coriell or ECACC 6 mo. – yr.
SMA Allison Ebert University of Wisconsin 2 lines, more in development Coriell Now/Later
SMA Kevin Eggan Harvard Several lines HSCI Later
Down Syndrome George Daley Harvard 1 line HSCI Now
Familial Dysautonomia Lorenz Studer Sloan-Kettering Several lines, 3 donors    
Rett Syndrome James Ellis University of Toronto Several lines, 1 donor James Ellis Now
Fragile X George Daley Harvard Several lines, 3 donors    
Control James Thomson University of Wisconsin 3 Lentiviral, 4 episomal WiCell Now
Control Margaret Keller Coriell Several lines Coriell Late 2010

While there are no standardized protocols yet, three common themes are emerging among scientists who generate iPSC lines. For one, most labs continue to use retroviral or lentiviral reprogramming due to the efficiency and ease of this method, rather than using newer non-integrating methods. For another, many researchers are making not only their iPSC lines publicly available, typically through a cell bank, but also the original fibroblast lines they used to generate the iPSCs. This allows other labs to employ their own method of choice to reprogram fibroblasts carrying mutations of interest. Finally, in addition to private labs working on iPSC lines, disease foundations, cell banks, and large consortia are also getting involved.

This is Part 1 of a four-part series.

To view commentaries, primary articles and linked stories, go to the original posting on Alzforum.org here.

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