REPORT – At the Saint-Louis hospital in Paris, Professor Jérôme Larghero and his team manipulate stem cells to produce cells of the heart or the retina.
In October 2014, Jacqueline Nguyen, 68, was hospitalized at the Georges Pompidou European Hospital in Paris (HEGP). Suffering from severe heart failure and the victim of a heart attack, the sexagenarian is forced to sleep sitting up, climbs the stairs with great difficulty and quickly feels out of breath. She needs to undergo coronary bypass surgery to improve the blood supply to her heart muscle. His tired heart is no longer pumping blood properly, due to the death of several heart cells.
Cardiac surgeon in this hospital, Prof. Philippe Menasché offers his patient to be the first person in the world to benefit from a stem cell transplant. They are “patched” on the heart to replace the failing cells.
One year after the operation, Jacqueline Nguyen “comes back to life”, dances with her little daughters, rides a bicycle, walks without being out of breath. And hope that many patients will be able to benefit from this cell therapy.
This world first is the result of twenty years of research carried out in collaboration with the team of Prof. Jérôme Larghero, director of the cell and tissue biotherapies department at Saint-Louis hospital, Assistance Publique – Hôpitaux de Paris. At 45, this doctor has devoted his entire career to cell therapy and the study of stem cells. He is at the head of one of the 36 French teams authorized to work on the embryo and embryonic stem cells.
Stored at – 180 ° C
It is in the buildings of the 17th century, from the Saint-Louis hospital, that the team to prepare the cardiac patch which was grafted on Jacqueline Nguyen. It is also within its walls that human embryonic stem cells are kept.
In the cryobiology area, they wait patiently in one of the dozens of nitrogen vapor tanks. In this room, the unit also stores prepared bone marrow transplants for patients with blood diseases, and umbilical cord blood bags the size of a bank card.
“They are cryopreserved at a temperature between -150 and -180 ° C so as to keep them almost ad vitam aeternam”, indicates Professor Larghero, lifting the lid of one of them. Because of the cold, the door creaks. This complaint is added to the uninterrupted whistling of the tanks and the incessant beeps signaling the presence of the nitrogen and oxygen indicators.
Jérôme Larghero, director of the cell and tissue biotherapies department of Saint-Louis hospital (AP-HP): ” It is very important that one is informed of the oxygen level in the room. When it goes below 17% you have two minutes to exit. “
Professor Jérôme Larghero selects a sample of bone marrow in a nitrogen steam tank. The Saint-Louis unit may have to export batches of embryonic stem cells to France or to the world. Source: Anne-Laure Lebrun / Pourquoidocteur
Find the right cocktail
Today, around forty research protocols are carried out in France. Embryonic stem cells offer great potential for treatment thanks to their ability to give rise to all cell types. But if this is true in the body, this promise has yet to be kept in the laboratory.
Because, these cells are not yet ready to reveal all their mysteries. Capricious, they don’t always do what is expected of them. Or at least scientists don’t always have the right codes to run them. “You have to find the right culture medium and the cocktail of molecules that can reproduce what happens during embryonic development, for each cell type,” explains Professor Larghero.
In Saint-Louis, a team tries to “make” heart cells from these stem cells, while another tries to produce eye tissue. These tests and cultures are carried out in one of the 8 “clean rooms” in a sterile environment.
The pressure, temperature and humidity are drastically monitored to avoid any contamination and deterioration of the cells. Scientists must also put on, in addition to their overshoes, an over-coat, a protective mask and a cap. “They even have to put on a second pair of gloves to handle under the hood,” slips the manager.
In one of the unit’s 8 clean rooms, a researcher handles stem cells from cord blood under the hood. Before she thawed them in a water bath (device in foreground). Source: Anne-Laure Lebrun / Pourquoidocteur.
Jerome Larghero : ” At each step of the manipulation you have to make sure that you got what you expected. So you have a series of checks to perform. “
A promising future…
But for now, few cells will leave these clean rooms to be transplanted into humans. Cell therapy for heart failure is the only one so far. Several French teams are following in the footsteps of Prof. Philippe Ménasché and Jérôme Larghero and launching into men.
In 2017, clinical trials will test the effectiveness of embryonic stem cells to treat skin or retinal disease. “We must remain aware that we are not yet able to reconstruct an organ from a few stem cells. We have arrived at an era of therapeutic application which aims to assess the safety and tolerance of these new approaches, ”he underlines.
In fact, many pitfalls persist. The first concerns first the amplification of the quantity of stem cells. “How do you get millions or even billions of cells from ten? This is what is at stake in the fundamental research currently being carried out, ”explains the specialist.
In Saint-Louis, teams are trying to find the best means of culture for these cells. Part of this research is carried out in a room of video microscopy plunged in the dark. “We may learn that cells prefer to grow in small wells than on flat surfaces, or are more prone to multiply on soft gels than on rock-hard surfaces,” he explains.
… but obstacles persist
Another major obstacle to the growth of cell therapy: the lack of funding. “France is not to be ashamed of this research, but it is finding it difficult to go beyond world premieres because we lack the investments enabling clinical research to be carried out on a larger scale”, affirms Jérôme Larghero.
The technique is indeed a very greedy field: it took millions of euros to develop cardiac cell therapy and treat a single patient, recalls the doctor.
Finding an industrial partner is no easy task either. It is for this reason that the Saint-Louis unit decided to restructure itself. A new building should soon be built in order to bring together a multidisciplinary team (biologist, clinician, researcher, engineer, etc.) in charge of the graft preparation platform and start-ups specializing in technological innovation.
Still, the hopes raised by embryonic stem cells are colossal and continue to generate enthusiasm among researchers. It took France 10 years to go from basic research to testing in humans. A giant leap while waiting for the next one.
Embryo research, what the law says
In our country, research on embryonic stem cells is authorized but supervised. Since the revision of the 2013 bioethics law, the texts provide “that no research on the human embryo or on embryonic stem cells can be undertaken without authorization”.
This supervision is provided by the Biomedicine Agency. Any research project must be the subject of a substantial file in which the teams must justify the use of these cells and the expected therapeutic benefit.
Authorizations last about 5 years. At the end of this period, a new application must be filed. However, not all works are accepted. Last year, 17 projects were authorized and 2 refused by the Biomedicine Agency.
In addition, France, like a majority of countries, prohibits the creation of embryos for research purposes. To conduct their work, researchers can only use supernumerary embryos conceived in vitro as part of medically assisted procreation and which are no longer the subject of a parental project. Parents’ consent can be revoked without cause by one or both members of the couple as long as the work has not started.
The United States, China, India, Israel or the United Kingdom have chosen to go further. They allow the cloning of embryonic stem cells.
At the Saint-Louis hospital in Paris, doctors manipulate stem cells to produce cells of the heart or the retina …
Posted by Why doctor on Saturday, April 9, 2016
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