Human adult stem cells are being used to cure cirrhosis and other serious live diseases. Another 15 people in Brazil on the liver transplant waiting list have been treated by cellular therapy with encouraging results. “We are still in a strictly experimental phase” underlined Luiz Guilherme Costa Lyra, hepatologist and coordinator of the study performed by Sao Rafael di Salvador Hospital, collaborating with San Raffaele Hospital of Milan. “We must clarify that this therapy is not available for any patient outside of the experiment, so it is useless for anyone to write us asking to get into the study.”
He continued, “Furthermore we must admit that the results are decidedly interesting and we intend to continue along this path.” The project, after having passed clinical safety and efficiency tests on animals and clinical safety tests on human beings, entered into the clinical testing phase on humans three years ago. Specialists at Sao Rafael di Salvador experimented on a group whose only hope was a liver transplant, but probably would have never received one due to the length of the waiting list. Cellular therapy allowed for a significant improvement in their conditions.
FROM ANIMALS TO MAN
The story begins just after the year 2000 with experiments on mice and rats with serious liver diseases. Milena Soares, who led this phase of experimentation said, “We worked with animals affected by serious hepatic fibrosis caused by infection, toxic substances, or alcohol (hepatic fibrosis is a condition in which healthy tissue is replaced by fibrous tissue, which causes a loss in liver function and tissue disorganization which can result in hepatic cirrhosis, editor’s note). The animals were treated with non-embryonic stem cells and responded well to the therapy, showing a significant improvement in their condition.”
In 2002, after clinical safety and efficiency testing on animals was completed, the researchers decided to give the go ahead to a first clinical safety experiment on 10 male volunteers on the liver transplant waiting list. Laura Ziller, president of Sao Rafael said, “This was only possible in Brazil because there is no obligation under the law to test primates before humans.” Riccardo Lyra specified, “The experiment was performed using autologous adult stem cells (obtained from bone marrow in the same patients) and gave good results in terms of safety and feasibility. We did not observe any side effects aside from some local pain and the patients also showed signs of improvement.”
The procedure consists in the removal some bone marrow from the iliac crest (the anterior protuberance of the pelvis) with a syringe and its transformation into tissue in the laboratory to isolate and manipulate the cells, followed by their re-infusion into the patient’s liver via the hepatic artery, all in a few hours.
The positive results of this experiment, compared with contemporary, analogous experiences from two research groups in Japan and Great Britain, have convinced researchers to make a “leap” towards therapeutic human testing (different from clinical safety tests).
Testing was performed randomly, meaning that after obtaining informed consent from 30 people on the transplant list,15 were chosen randomly and given the treatment while the other 15 continued receiving normal therapy and were used as a control group (a basis for comparison). “The patients were followed for one year,” explained Lyra. “The results were significant in the first 90 days, during which all indexes considered for patient evaluation clearly improved, which was then followed by a progressive return towards their initial conditions.” Was it a partial success? “From an experimental point of view, no, because the results we obtained were substantial. Now we are thinking about further experiments to verify if it is possible and to what extent, to maintain or increase their improvements.” Could this include a second stem cell initiation?
“It is possible but it is not certain,” said Ricado Ribiero dos Santos, scientific director of Sao Rafael. “We must clarify that injected stem cells do not transform into liver cells. Instead, they stimulate local stem cells to differentiate and mature into liver cells, replacing the lost cells. For this reason it may be unnecessary to resort to external stem cells for support, and it could suffice to use other stimuli. I believe that we should move towards a complex, integrated therapy. It should also be stressed for obvious and shared ethical reasons, that we treated extremely hepatically compromised patients. If we had treated people in better condition, we probably would have obtained more significant results.” The next step? “Like I said, further experiments on patients with liver diseases then another experiment for Chagas disease, a serious form of cardiomyopathy.”