Induced Pluripotent Stem Cells do not Form Neural Stem Cells as well as Embryonic Stem Cells

Induced pluripotent stem cells show tremendous promise for regenerative medicine. However in a February 15th article in the Proceedings of the National Academy of Sciences, showed that induced pluripotent stem cells (iPSCs) were inefficient at forming the cells of the brain in comparison to their embryonic stem cell counterparts.

The senior author of the article , Su-Chun Zhang, (professor, University of Wisconsin-Madison School of Medicine and Public Health), said:  “Embryonic stem cells can pretty much be predicted,” and “Induced cells cannot. That means that at this point there is still some work to be done to generate ideal induced pluripotent stem cells for application.”

This study compared the ability of five different embryonic stem cell lines to 12 different iPSC lines to form nerve cell precursors.  Embryonic stem cells are considered the “gold standard” for all pluripotent stem cells, which are cells that can differentiate into all of the 220 cell types in the human body.  Zhang’s group found that the induced cells differentiated into progenitor neural cells and further into the different kinds of functional neurons that make up the brain, but they did not faithfully reproduce all the differentiation capabilities of embryonic stem cells.  This suggests that there are unknown factors at play that may limit the use of iPSCs when it comes to modeling diseases in the laboratory.  Such unknowns would also limit their use in clinical settings for such things as cell transplants.

Despite their unpredictability, Zhang notes that iPSCs can still be used to make pure populations of specific types of cells, which makes them useful for some applications like testing potential new drugs for efficacy and toxicity.  Zhang also noted that the limitations identified by his group are technical issues likely to be resolved relatively quickly.  “It appears to be a technical issue,” said Zhang.  “Technical things can usually be overcome,” he added.

This is very possibly a technical issue that is due to our inability to properly manipulate iPSCs to form nerve cells.  However, if the same protocols that drive embryonic stem cells to form nerve cells are used on iPSCs, they only form nerve cells poorly.  There are probably other protocols that can do just this.  We just haven’t found them yet.

Also, it is worth mentioning, that the ability of iPSCs to differentiate into neurons is probably a line-specific property.  Therefore if these lines to not form lines effectively, then perhaps other lines do.


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Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).