A new alternative for transplants: 'buds' liver

After 15 years of promises, disappointments and political obstructions, the stem cells begin to yield results, and Japan and is emerging as the world's leading brand of regenerative medicine. After announcing last week the first clinical trial to regenerate the retinas of blind Japanese biologists break the bank today with some buds of human liver in the laboratory manufactured from iPS stem cells and, according to those familiar with the investigation, represent a crucial step towards a new class of treatment for liver patients who die in the line of transplants.

The technique may take about 10 years to reach the clinic, but it represents a proof of principle of the fundamentals of the emerging regenerative medicine: the manufacture of organs and tissues to be transplanted into patients to treat a wide range of currently incurable diseases. The discovery of iPS stem cells by Shinya Yamanaka, last Nobel Prize in Medicine, has prompted Japan to put their best science in the development and clinical application of regenerative medicine.

IPS cells are the great promise of this field of biomedical research. The main alternative, for all that is known so far, are embryonic stem cells (ESC initials of his English name embryionic stem cells ), which were in 1998 the big trigger for this field of research, but also have earned the religious condemnation by human embryos obtained two weeks prior to implantation in a womb. IPS cells, however, are obtained by delaying the clock (reprogramming, in the jargon) of simple skin cells to regain their ancestral nature of stem cells.

Takanori Takebe and colleagues from the Faculty of Medicine of the University of the City of Yokohama in Japan presented tomorrow in Nature an inquiry call to have a significant scientific impact in the near future. They managed to generate for the first time "three-dimensional vascularized human organ", specifically a liver from iPS stem cell cultures. To prove it works have transplanted mice humanized, or prepared for not rejecting the implant. But the transplanted liver is human as human as the person that was extracted a skin cell to become, with the techniques of the Nobel Yamanaka, a crop of iPS cells.

The clinical application of this technique is not immediate: Takebe himself expected to reach in 10 years, which is the scientific way to say "do not know". The yolks of liver Japanese researchers have generated are entirely human, but getting permits for a patient transplant still requires overcoming many protocols, and some very important.

First and foremost, scientists will have to demonstrate that risks from iPS cells (genetic instability, drift potential cancerous) do not outweigh the benefits of the implant. In experiments with mice, Takebe and his colleagues have not detected any of these problems, but obviously not enough.

The director of the National Transplant Organization (ONT), Rafael Matesanz, considered "very interesting" work of the Japanese. "Although iPS cells are a line of research among others," he points out, "and until we know what is the best you have to follow all parallel, including embryonic stem cells and biomechanical structures, such as those being exploring for artificial trachea."

If this technique or similar reached clinical practice, what is its importance in a country like Spain, leader in organ donation? "Right now there are 1,100 patients on the waiting list for liver transplantation, and between 6% and 8% will die waiting," says Matesanz. That's from 60 to 80 deaths, but the foremost expert in transplantation in this country emphasizes that this figure should not be taken as an indication of the usefulness of a liver transplant source. "If there were twice as livers, demand would also double," says Matesanz.

Physicians and surgeons are well aware of how much supply of donor livers-whether living or dead, is available and, as much as Spain leads the ranking donor world, there would always be plenty of scope for growth of transplants. For example, spread cancer patients are excluded as recipients when donations are scarce, but increasingly would be included if the health system find a new source of organs, or things that work as organs.

Potential applications of the buds of Japanese liver not limited to future transplants. Matesanz indicates two possibilities, probability, may come before such interventions. "One is to test new drugs," says the director of the ONT. This is a particularly interesting possibility with the liver, which is the organ that metabolizes foreign substances, including drugs. To examine the toxicity of a new molecule in cultured buds could substantially facilitate liver tests must overcome to reach-or not-a clinical application.

The second possible application is short-term treatment with cultured hepatocytes, or liver cells. Not with buds or three-dimensional bodies, but with mere cultured liver cells which are one of their constituents. "It's a rare treatment option, but that is already used in clinical practice," says Matesanz. It is sometimes used to keep a patient alive until it reaches the organ that will save the life or to treat children with metabolic deficiencies or hereditary diseases which lack an enzyme or biological catalyst. Hepatocytes provide in this case normal enzyme which lacks the child.