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Biomedicine and Molecular Biology

The hidden face of stem cells

Some seek the elixir of eternal youth. Others, the Holy Grail. And the laboratories of molecular biology and genetic engineering of the world are full of “Indiana Jones” in search of the key to decipher the behaviour of human cells. But after finding embryonic, adult and pluripotent stem cells, now scientist find themselves cruising in a sea of doubts.

Ànnia Monreal | 13 july 2009

“It is not clear which is the safest method for a future application of stem cells”. “What are the advantages and disadvantages of induced embryonic and pluripotent stem cells”. “We do not know very well yet how to pass from one differentiating cell to another in a format that is 100% safe.” These are some of the question marks that the scientists ask themselves during the congress of the International Society for Stem Cell Research (ISSCR), recently celebrated in Barcelona.

They know which way to follow, that genetic therapy will be a solution in a few years time which will revolutionise medicine. But they do not know how to save all the pitfalls presented. Konrad Hochedlinger, professor of the department of Stem Cells and Regenerative Biology from Harvard University, summarised like this the main challenged: “We need to know if the cellular reprogramming with induced pluripotent stem cells is safe, as well as establishing functioning models for each disease in order to create stem cells that are as efficient as possible”.

Regenerative medicine

The hopes resting on therapeutic possibilities of stem cells have two very clear pathways. “to repair the damaged tissues and to solve genetic diseases”, as pointed out by Thomas Graf, coordinator of the Differentiation and Cancer programme from the Centre de Regulació Genòmica de Barcelona (Genomic Regulation Centre of Barcelona, CRG). For now though “the only treatments that have really been tested and that work are the transplant of haematopoietic and skin cells”, indicates Edwin M. Horwitz, paediatrician at the Oncology centre from the Children’s Hospital of Philadelphia.

“We are advancing very slowly”, Graf recognises. “Each type of cell that we want to generate has its specific problem”, he adds. And hence the saying: each teacher must follow his own book of instructions, even though everybody is chasing the same thing, from Beijing to Boston, passing through Barcelona, Edinburgh, Munich, Singapore, Lausanne, San Francisco or Kyoto.

When Shinya Yamanaka, director of the Centre for iPS Cell Research and Application from the University of Kyoto, decided to reproduce conversely the development of a cell (from specialized organism to stem cell) and discovered induced pluripotent stem cells (iPS) in 2006, research saved the ethic loophole. Laboratories were able then to work with stem cells without sinning, but the tests with mice showed that the use of these caused tumours in the majority of cases.

Gene therapy will be a solution in a few years time and it will revolutionise medicineSince then one tests, tries, understands, learns and tries again. The ISSCR congress served to show that groups exist that work to convert a specific cell into another specialized one without resorting to iPS. Others try to understand the mechanisms of the transcription factors (proteins that activate the genes and determine then the function of a cell) they evolve until a differentiate cell is created. And some, like in the case of Juan Carlos Izpisua, director of the Centre de Medicina Regenerativa de Barcelona (CMRB, Centre of Regenerative Medicine in Medicine), try to find “how to better understand the cellular regeneration mechanisms and why some animals can do it and the human being cannot”. Discovering how certain amphibians and reptiles are capable of recovering their tails when cut is one way “that is still beginning”, according to Thomas Graf.

Desperate sick people

If the scientists lack a fixed course, what certainties can be transferred to the patients? The disproportionate publicity about the scientific advances with stem cells has tumbled the expectations of many patients. “It is clear that people have a 5% chance to survive if they can hang onto this percentage and somehow seek a solution”, admits Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease in San Francisco. And this discovery has woken up the so called stem cell tourism. There are cases in China, Latin-American and European countries with little regulation on the issue.

It’s about clinics that promise miraculous treatment thanks to the use of stem cells, not scientifically proven, to cure genetic pathologies. And there is more. Together with these ailments a pathway has opened which says it uses stem cells applied to cosmetic treatments. This is uncontrollable” Yann Barrandon points out, director of the Dynamic Laboratory of stem cells of the École Polytechnique Fédérale de Lausanne.

“The scientific community lacks powers to regulate, define and pin point the centres that do not work correctly”, warns David T. Scadden, co-founder of the Harvard Stem Cell Institute. “Therefore we have opted to inform as much as possible”, he continues. A sample of this is the guide of the ISSCR webpage, where the steps are given to contrast the seriousness of a professional.

Anna Veiga is more combative, she is the director of the Bank of cellular lines from the CMRB: “There should be a list of the clinics that offer miraculous treatments that have not been tested”. But the lack of transparency of these countries and of the patients, “that travel without consulting their own GP”, Veiga points out, makes it difficult to create a unique register.

To the traffic of people that are looking for an inexistent solution another issue is added: if the treatment does not function and it harms the patient, who is responsible? Maybe it is not so much a case of trying to find an improvement or a cure, but to accept that, despite the technological advances, medicine is not yet capable of solving all the reaction of the human body. Even though Shinya Yamanaka is optimistic: “I think that in five years time it will be possible to have stem cells from iPS cells” that do not harm the organism.

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