Notable Papers: An Easier Way To Make Stem Cells?

Stem Cells

We’ve talked about work out of the RIKEN Institute before here on Webvision.  The work that comes out of there is clever and often unconventional.  The latest work from the RIKEN that seems to have gotten a bit of attention is two recent papers from Haruko Obokata and colleagues, here and here that discuss almost inconceivably simple approaches to generating stem cells out of adult, differentiated blood, fat, muscle and brain mouse cells.  The approach essentially immerses the cells in an acidic solution for a half hour to induce a state of cell stress and subsequent induced pluripotency allowing them to recapitulate mature, differentiated tissues of a variety of cell types, including a reported blastocyst.  Granted, there are a variety of ways to collect and harvest stem cells, but these approaches present a variety of both ethical and logistical confounds.  So, this approach could solve a number of problems related to collecting and harvesting stem cells.

The other notable thing about this study is how elegant the screening method was.  The authors used GFP tagged Oct4 genes to note when cells had reached pluripotent status.  These GFP expressing cells were then indicators of induced pluripotency in harvested, differentiated cells that underwent stress through acid immersion.  Since only approximately 25% of the cells that underwent acid immersion survived, this approach allowed the investigators to see which of those remaining cells exhibited Oct4 gene expression revealing pluripotent stem cell status.  Other assays backed up these determinations of pluripotency including teratoma assays as well as the creation of chimeras.

If this approach proves a viable technique to generating stem cells, work in stem cell based vision rescuing therapeutics (as well as many other therapeutic applications) could be dramatically facilitated as labs exploring stem cell therapies in vision rescue are currently having to invest large efforts in using existing approved stem cell stocks or isolating stem cells through labor intensive methods.

Update 03/10/14:

The Wall St. Journal is reporting that one of the co-authors of this study said the research contained “crucial mistakes” and RIKEN is weighing whether to retract the papers.

 

Update 07/02/2014:

Nature has announced that the papers have been retracted.

 

Update 09/23/2015:

The STAP approach has been completely refuted.

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Interesting Article: Mechanism of RPE Cell Death in α-Crystallin Deficient Mice: A Novel and Critical Role for MRP1-Mediated GSH Efflux

RPE

I ran across an interesting paper in PLOS One published back in March of 2012 by Parameswaran G. Sreekumar, Christine Spee, Stephen J. Ryan, Susan P. C. Cole, Ram Kannan and David R. Hinton.  This manuscript looks at a mechanism of retinal pigment epithelium (RPE) cell death with notable findings identifying therapeutic targets for disorders that involve the RPE cells.

The authors tested whether α-crystallin has a protective effect that is influenced by changes in glutathione (GSH) content while exploring the mechanism of glutathione efflux from the cells.  Interestingly, they found that the multiple multidrug resistance proteins (MRP) were expressed in RPE, particularly MRP1 and that it is MRP1 that mediates GSH (reduced form) and GSSG (oxidized form) efflux from the RPE cells.  In addition, they noted that inhibition of MRP1 makes RPE cells resistant to oxidative stress induced cell death pathways and conversely, over expression of MRP1 renders them more susceptible to oxidatively induced cell death pathways. Finally the authors note that α-crystallin’s antiapoptotic function is mediated by both GSH and MRP1.

Continue reading “Interesting Article: Mechanism of RPE Cell Death in α-Crystallin Deficient Mice: A Novel and Critical Role for MRP1-Mediated GSH Efflux”