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
|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|
|PD||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/
|10-15 familial||Coriell||Early 2011|
|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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