The day of plenary is the most enjoyable in my view including at ISSCR 2015 on the first day with a Yamanaka talk. You don’t need to make the choice between sessions and the judgement on the viability of shifting sessions versus staying put and listening to the slightly less relevant.
ISSCR 2015 plenary was, as to be expected, full of the big names, the affectionately known Rusty (Fred Gage), Jonas Frisen (one of the smartest MD PhDs I have ever met) and of course Shinya Yamanaka. In deciding which talk I wanted to highlight it is somewhat cliché to go for the Nobel Prize winner but I just can’t help it, he is just such a great guy.
I first met Shinya at Karolinska Institutet, Stockholm, Sweden, when he was giving a presentation (no doubt an interview for his Nobel Prize). In association with this trip he was interviewed in our lab space where he divulged that he got into research as he didn’t think he was a very good orthopaedic surgeon, he wanted to do something where he could help people!
So, I was very pleased to see that his ISSCR 2015 talk was divided into 3 sections;
- immune matching of pluripotent cells
- differentiation and purification of desired cells types
- pre-clinical testing of stem cell therapies
What this tells me is that Shinya is truly devoted to helping people. That he is not just thinking about the first step or the last step of stem cell therapies but the entire process, each step as important as the next and the previous. It is not enough that he has a Nobel Prize and could spend the rest of his career studying the mechanisms of reprogramming, he wants to drive his technology to the patients. What a star!
The first part of the talk outlined his work into HLA haplotype matching with regard to homozygous individuals. With a current Japanese focus, just one donor homozygous for the most common HLA haplotype would be sufficient to provide immune matched cells to 10% of the Japanese population. 10 homozygous donors with other common haplotypes would cover 50% of the population and 140 homozygous donors would cover 90%. With 1:1000 individuals showing a homozygous phenotype AT LEAST 140,000 individuals would need to be HLA screened, with this number falling drastically short on the fact that a specific repertoire of HLA haplotypes would be needed. So Shinya and his team are scanning the blood donor and cord blood bank stocks to find their golden donors. A huge task, with huge reward.
For differentiation and sorting Shinya’s team have developed a method called miRNA switch. The technique is mainly aimed at those cell types for which we do not have good cell surface markers for FACS sorting. Basically expression of two fluorescent proteins indicates transfected cells, which upon differentiation to the desired cell type, will lose expression of one of the fluorescent indicators under the control of a cell type specific miRNA. These single positive cells can then be sorted or selected with chemical resistance. Simple and elegant though may require significantly larger numbers of cells, dependant on transfection efficiency.
Finally, my favourite iPSC master showed data from a pre-clinical study into Parkinson’s Disease transplantation of Corin+ dopaminergic neurons. For this section Shinya was very careful to acknowledge his collaborator Professor Jun Takahashi, and continued through the section to present the work as ‘he did’ rather than ‘I did’ or ‘we did’. In the study they were able to show that sorted iPSC derived Corin+ dopaminergic neurons transplanted into monkey brain gave functional recovery of Parkinson’s Disease and survived for at least one year without a reduction in graft size and without tumor formation. Interestingly, whether the original iPSC were from diseased or non-affected individuals, similar rescue was seen, arguing for autologous therapies from the diseased individual. These results were setting up for the exciting step of testing these human cells in human clinical trials beginning within the next 2 years.
While Shinya may be the big name, his humility and genuine desire to make a change in the lives of patients is a great inspiration. His continued dedication to the cause in light of his earth shattering appearance onto the stem cell stage is a testament to a great guy. Japan is definitely the space to watch for a dedication to stem cell therapies (including liberal regulatory standards), and I’m sure along with Shinya they will continue to drive the field forwards both at the basic and clinical level.