Making IPS cells more efficient? New studies shed light on the reprogramming process

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A recent editorial in Nature highlighted the murky landscape of patenting induced pluripotent stem cell (IPSC) discoveries, ultimately concluding that patent thickets might stand as one of the central challenges to the smooth patenting of IPSC technologies. This comes on the heels of the controversial news that Dr. Shinya Yamanaka, professor at Kyoto University who shared the 2012 Nobel Prize in Physiology or Medicine with Dr. John B. Gurdon for their discovery of the ability to reprogram adult stem cells to become pluripotent, had her patent for the discovery challenged by an unknown entity called BioGatekeeper. This news is still unraveling, and little else is known about the challenger or what this will ultimately mean for the technology.

On the subject of IPS cells, two interesting papers have appeared in recent weeks which aim to improve on the technology described in Yamanaka’s patent.

One of them, by the lab of Miguel Ramalho-Santos, associate professor of obstetrics, gynecology, and reproductive sciences at University of California – San Francisco, addresses issues that commonly arise during reprogramming of adult cells and result in low reprogramming efficiency. The authors reported on the discovery of “reprogramming barriers”, in the form of genes which regulate, in their own words, transcription, chromatin regulation, ubiquitination, dephosphorylation, vesicular transport, and cell adhesion. These are, they report, disintegrin and metalloproteinase proteins. However, while these barriers appear to prevent complete reprogramming, they also appear to protect the integrity of adult cells, and have furhter protective effects. The study, titled “Systematic Identification of Barriers to Human iPSC Generation” is published in Cell.

Along similar lines, another new collaborative study published in Stem Cells Translational Medicine titled “Removal of Reprogramming Transgenes Improves the Tissue Reconstitution Potential of Keratinocytes Generated From Human Induced Pluripotent Stem Cells” by Ken Igawa’s lab at Tokyo Medical and Dental University and collaborators at Osaka university, compared the efficiency of reprogrammed human skin cells after removing reprogramming transgenes to reprogrammed cells containing the transgenes. Interestingly, after the cells were differentiated into keratinocytes, the authors observed that reprogramming material-free cells were functionally and morphologically more similar to normal human keratinocytes than cells still containing the genetic reprogramming material. The implications for clinical use are potentially significant, although further investigations should be untertaken to elucidate the exact long-term effect of the removal of such genes. Moreover, studies on additional cell lines should also be carried out and investigated.

To answer the question in the title, can we make IPS cells better? Taken together, these two studies highlight the significance of the presence of genetic material in directing reprogramming and the subsequent fate of reprogrammed cells after differentiation, and it will be interesting to see how they impact further growth of the prolific IPSC field.

 

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