stem cells in their environment

Happy Birthday iPSCs  - You are ten years old now!

12 December 2016
By Annie Kathuria

First of all, I would like to wish them a Happy Birthday from myself. For those of you who don’t know what exactly iPSC’s are, they are induced pluripotent stem cells. iPSCs are adult cells that have been genetically reprogrammed to an embryonic stem cell–like state. This is generally achieved by enforcing the expression of four genes Oct4, Sox2, Klf4, and cMyc (also known as OSKM factors or the Yamanaka factors). These cells were first described in a ‘Cell’ paper (which has over a whopping 15,000 citations so far!) ten years ago by the Japanese scientists Drs Shinya Yamanaka and Kazutoshi Takahashi. To celebrate their tenth year anniversary, the science journal Cell along with other co-partners organised a Symposium in the sunny city of Berkley in California. I was one of the lucky ones to be chosen to present a poster at this meeting. Here, are some highlights from the conference:

Moving from basic to translational research: The discovery of the iPSCs ten years ago brought about the question; can these cells be used for translational research? Moreover, can they be transplanted into humans?  Dr. Yamanaka answered this question mentioning his collaboration with Dr. Takahashi to treat the first patient affected by advanced macular degeneration. It took them two years to create iPSCs and perform the necessary quality checks on the cell lines generated such as screening for single nucleotide, copy number and structural variations, DNA methylation and single cell gene expression. Once the iPSCs were deemed usable from a genetic standpoint, quality checks were performed on iPSC-derived retinal pigment epithelial (RPE) sheets. For this, they checked the appearance and structure of cells, the live cell ratio, RPE-specific gene expression, purity, stem cell markers, bacteria, fungus and microplasma tests. After all of these meticulous screenings, they were able to do the transplantation in only one patient. The second patient trial was suspended due to failure of the patient’s iPSC to pass the genetic evaluation.  Others have also tried to translate the use if iPSC’s in various neurological disorders: Hideyuki Okano presented revolutionary work on spinal cord injuries; Lorenz Studer worked on Parkinson's Disease and Kevin Eggan presented work that is leading to promising clinical trials for ALS.

Stem cell research is expensive and time-consuming: As a stem cell scientist myself, I can vouch that stem cell work is laborious, time consuming and expensive. As Dr. Yamanaka mentioned, it took more than 50 people and about two years to make the stem cell that could be used in clinical trials. Another example which demonstrates the labour-intensive nature of stem cell research is, Juan Carlos Izpsua Belmonte’s work on transplantation of human kidney progenitors into pigs which took the combined effort of more than five research associates. However, hope is not lost – dedicated scientists continue to persevere and push boundaries to improve stem cell work and make systems more efficient.

Ethics: One of the most daunting questions in science is "Ought we?". On the first night of the symposium there was an ethics panel. The top scientists in the field tried to answer questions such as how genome editing affects stem cells, is transplantation the future of iPSCs and how can stem cell banking be improved and shared across international borders. Even though there weren’t any clear-cut answers to the questions, at least the discussions have begun.

All in all, it was great opportunity to learn and discuss the past, the present and the future of stem cells.

 

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