Stem Cells

Stem cell biology is possibly the most controversial area of research in the life sciences, both within the research community as well as in the public eye. What exactly are stem cells? They are cells that have the choice between forming another stem cell (self-renewal) or a daughter cell which will differentiate into a specific cell type. A real stem cell has this choice every single time it divides (image from here). There are several types of stem cells: the most versatile are the pluripotent stem cells, because they can differentiate into any adult tissue, including the germ-line. The more restricted stem cells are already lineage-specific, such as haematopoietic stem cells, which form all constituent cells of the blood.

Earlier this year, a group based at the RIKEN institute in Japan claimed to be able to reprogramme differentiated, adult cells into pluripotent stem cells by simply stressing the cells using a weak acid (Obokata et al. (2014)). These cells are known as STAP (stimulus-triggered acquisition of pluripotency) cells and were an immense breakthrough – until then cells could only be reprogrammed either by transferring the nucleus of the adult cell into an enucleated oocyte (without its own nucleus) or by forcing the expression of certain proteins (transcription factors) that regulate pluripotency. Immediately scientists around the world tried to reproduce these results because it provided a much faster method of working with stem cells. However, essentially nobody could replicate the findings. A crowdsource page was set up to allow researchers to share their experiments online and eventually this led to an investigation of the lead author’s work: the RIKEN institute found that Obokata had falsified/fabricated her results, which is gross scientific misconduct. A few months after this the paper was retracted by Nature, but it is still accessible online.

I don’t claim to know what led this research group to become so desperate that they knowingly published false results, which subsequently caused hundreds of other scientists to waste their time on something that wasn’t going to work. Of course I do not think that such behaviour is justifiable. However, something that many people aren’t aware of is that Obokata’s supervisor hanged himself early this August at the RIKEN institute (press release here). I can’t even begin to imagine how many peoples’ lives have been damaged by this affair. It makes me wonder whether there is something fundamentally wrong with the way research is conducted – in a highly competitive environment! – such that it can become too much for a single person to bear and drives him/her to suicide. [I expect that East Asian scientists are probably more likely to commit suicide than American scientists, for example, due to cultural differences.]

But to end this entry on a somewhat happier note: a couple of weeks ago a group published in Cell that they could convert human pluripotent stem cells into human pancreatic beta cells, the cells which secrete insulin in the pancreas (Pagliuca et al. (2014)). After several steps of conversion in vitro they obtained cells that looked like and behaved like beta cells, which responded to glucose and could secrete insulin. To test whether they also functioned in vivo, they transplanted these cells into diabetic, immunodeficient mice (which do not reject the human cells) and they found that the mice could control blood sugar levels (image from the paper).

This finding has enormous implications because it means that patients with type I diabetes, in which beta cells are destroyed due to autoimmunity, might in future be treated with their own reprogrammed stem cells.

References:

Obokata H, Wakayama T, Sasai Y, Kojima K, Vacanti MP, Niwa H, Yamato M, Vacanti CA (2014) Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature 505: 641-647

Pagliuca Felicia W, Millman Jeffrey R, Gürtler M, Segel M, Van Dervort A, Ryu Jennifer H, Peterson Quinn P, Greiner D, Melton Douglas A (2014) Generation of Functional Human Pancreatic β Cells In Vitro. Cell 159: 428-439