"Pancreas, lung or thyroid are candidates for the future" - The País.com (Spain)

Takanori Takebe

just touch the sky of science with only 26 years. Together with his team at the University of Yokohama (Japan) has created microhígados (primitive liver structures, or buds) of four millimeters. It has done manipulating iPS stem cells (the great hope of regenerative medicine, normal skin cells reprogrammed to become any cell lineage). The pads serve two key features for the design of laboratory organs: are vascularized and are three-dimensional. In mice, these grafted miniórganos operate smoothly and (produced proteins characteristic of the organ), which represents all hope for the manufacture of transplant organs in the future. Nature published the research Thursday with Takebe as the first author of the article.

Through email, the young scientist responds to questions posed by El Pais and tells it all started with a stroke of luck.

Asked . How does he found the key to developing liver yolks?

Reply . Two years ago, worked in hepatocyte cultures derived from embryonic stem cells, endothelial cells of umbilical cord vein and mesenchymal stem cells. On one occasion, one of them grew too, but instead of throwing it occurred to me to join them to see what happened. I had little hope that some of that out. And yet, I watched reproduced the genesis of organs. When handling gave rise to three-dimensional structures reminiscent liver formation in the embryo. At that time I did not use hepatocytes derived from iPS cells, but was convinced, as it were, that would also work if used. It cost me hundreds, if not thousands of trials, and more than a year to find the right growing conditions, nutrients and ratios between cells.

P. Why the liver?

R. Due to my personal experience. While studying medicine at the University of Columbia (USA) I specialized in liver transplant surgery. There I saw many patients, including many children, have no access to grants and die while waiting. I got to witness even cases of transplant tourism [sale of organs to foreigners].

P. Does your group intends to apply this technique to other organs in the future?

R. Yes The pancreas is a promising candidate. Also the lungs or thyroid. Bodies want to address [as liver] develop from the endoderm [one of the three layers of cells are formed in the early stages of embryonic development, from which it creates the digestive, respiratory and viscera ].

P. the heart also?

R. We believe it is possible, but this body has a different cellular origin [the mesoderm, one of these three layers] and has a relatively distinct development process.

P. You have developed liver buds about four millimeters. Do you plan to make larger tissues?

R. This would require an internal irrigation capillary system for the arrival of nutrients and oxygen, and thus prevent the structure necrosara. We are looking for partners to develop this type of irrigation in vitro of the buds that we have created in order to be able to increase the scale.

P. When calculated to arrive early clinical trials to implement its human research

R. For about seven years. The biggest challenge we face is to get a lot of buds [Takebe underlines and bold mark these last four words in the answer] to transplant patients, since the liver is one of the largest organs in the body : contains more than a billion hepatocytes [yolks are three to four million cells]. We need to produce a sufficient quantity at a reasonable cost. We propose a therapy that is transplanted liver in gestation (buds), other organ transplant or mature cells. Do not forget that 4,000 U.S. patients die waiting for a liver: it is easy to imagine the amount of liver aggregates to be produced to save them. [In Spain between 6% and 8% of the 1,100 patients who need a liver right now will die before receiving].

P. Are you concerned about security, there is a risk that the tumors develop microhígados

R. This is a very important issue that we carefully evaluate. So far we have been monitoring the mice six months we have tried and we have not observed the formation of tumors or teratomas. Therefore, we are very optimistic.

P. What are the advantages of iPS cells compared to embryonic?

R. You can easily develop pluripotent stem cells from adult cells without ethical misgivings.

P. First the Nobel Prize for Medicine in 2012 by Shinya Yamanaka iPS, then the announcement of the first clinical trial with these cells led by Masayo Takahashi a week ago, and now their work . Is there any reason that Japan is emphasizing in this plot?

R. I do not think that we are more powerful than the United States or Britain.

P. Is youth a virtue when dealing with novel or risky strategies?

R. I’m not sure, although it is true that I may apply ideas that older people consider strange.

P. regenerative medicine has finally found the way with iPS after setbacks in embryonic stem cells?

R. I think so. Anyone can now easily access and work with pluripotent stem cells by iPS.