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. (See Part 4 of this series for a discussion of these issues.)

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
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/ 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. For more on each of these points, and details on disease-specific iPSC lines, see Part 2, Part 3, and Part 4 of this series.—Madolyn Bowman Rogers.

This is Part 1 of a four-part series. See also Part 2, Part 3, and Part 4. Download a PDF of the entire series.