“In the future, I see young people saving their cells to use them as regenerators in old age”

2023-09-18 01:50:22

SONIA MORENO

Los Alczares

Updated Monday, September 18, 2023 – 01:50

For Robert Sackstein, doctor and researcher, our body keeps the fountain of youth in mesenchymal stem cells.

Robert Sackstein is vice president of medical affairs at Florida International University in Miami and professor emeritus of medicine at Harvard UniversitySEHH

When I was a student at Harvard University, Robert Sackstein He began to have contact with bone marrow transplants; then I found that one in four patients who receive the treatment dies shortly after, due to failure of the graft: the transplanted cells they could not find their way through the bloodstream to the bone marrow.

Thus he began to delve deeper into the molecular mechanisms that guide cells in this process, for which he had the help of the Nobel Prize in Medicine and pioneer in the development of transplantation as a mentor. Donnall Thomas. Sackstein’s research has culminated in a technology based on the modification of cell membranes through the insertion of a GPS that allows mesenchymal stem cells to be directed to damaged tissues.

Like the cells he works with to one day cure osteoporosis, this doctor and researcher also seems to have a GPS that has guided his career since he was a child. Despite the vicissitudes of his childhood and youth, or perhaps because of them, he never abandoned an early fixation on treat the disease but “always understanding how”. Currently professor emeritus at Harvard and vice president of medical affairs at Florida International University in Miami, Sackstein is proud of the influence of his Cuban family, with Spanish ancestry, in this interview we did with him in Los Alczares. Here he has co-directed a Advanced Therapies course organized by the Spanish Society of Hematology and Hemotherapy (SEHH), the Carlos III Health Institute and the University of Murcia.

No one will assume from his name that he has a lion grandfather.On my father’s side I have Jewish family from Lithuania and Germany, and on my mother’s side, from Spain. My parents met in New York, where my father was born. He had been with the US Army in World War II, and he considered himself a citizen of the world. My mother was a Cuban pianist who was there studying with Claudio Arrau, the best interpreter of Beethoven, with a scholarship from the Batista government. They met in the late 1940s and got married there, but my mother wanted to have her children in Cuba, so they settled in Havana, and that’s where I was born. I am Sackstein Guerrero, although I lost my second last name when I arrived in the United States. My maternal grandmother’s family comes from Seville and the Canary Islands, and My maternal grandfather was born in Villafranca del Bierzo. She left for Cuba when she was 20 years old and never returned to Spain, but she always had her very much in mind; She told us many anecdotes about his hometown and I grew to know him very well. So much so that a few years ago I went to see the town and it was just as I described it.Is it true that your father had to leave Cuba because they thought he was a CIA spy?That’s right. My father was the vice president of the American Legion, where there were army veterans. In 1960, they shot the president of that organization, a good friend of my family, and they told my mother that my father would be next. the same Ch Guevara wanted to shoot him. It was knowing it and fleeing to Miami with a suitcase. I was three years old about to turn four. Although my parents told me that we were going on vacation, I remember my mother crying a lot. She didn’t understand her sadness. I see her as if she were yesterday. A few years ago, I met up with one of my then neighbors in Havana and he confirmed that shortly after we left home, about thirty soldiers arrived, with trucks. He, who was an eight-year-old boy, and his family were in hiding for a month fearing that they would also come for them.Already exiled in Miami, you were a very precocious child; He immediately knew that he wanted to be a doctor.When we arrived, 19 people lived in a three-bedroom house. My grandmother always went to sleep at 3 in the afternoon for a while, because her head hurt a lot, and I thought it was because of the trouble she gave her, since she was a very active child. Then we found out that she had arterial hypertension. At that time there were very few treatments and I promised him that I would find one for him. That’s how, at age 12, I started going to the University of Miami library to study about the disease. At that time, an expert in hypertension, Professor Murray Epstein, I was doing research at that university. I asked my father to help me get to know him and we made an appointment with one of his assistants. I remember that he was very surprised when he saw me, because he didn’t imagine that I was a 13-year-old boy. They couldn’t offer me a job working for someone my age in the lab, but my father insisted: “My son knows how to work hard.” And they let me volunteer. He was in charge of cleaning the rat boxes for the experiments. He cleaned them thoroughly, with a toothbrush. He left them so clean that the data collected was free of any contaminating element and the experiments progressed very quickly. They were soon able to begin clinical trials with the drug, which turned out to be captopril. As thanks for the effort, They allowed me to include my grandmother in the study. Then I knew that he wanted to be a doctor, but also work in the laboratory.That determination in such a young person is striking. Did she have any influence on her family?One guy was a surgeon, but what I wanted was to cure as a researcher, to do science. My mother taught us music; I soon saw that she was not my thing, unlike what happened to my sister, who had a lot of talent. On the other hand, I had much more facilities for science. Also, when I was little I was impressed by the fact that a cousin of mine lost an eye to congenital glaucoma. How can it be that medicine is not able to save an eye?, he thought. That reinforced my goal of being a doctor and researcher.He has certainly fulfilled it, because throughout his career he has always combined clinical practice with research. He is now focused on developing a somatic cell therapy to treat osteoporosis. At what point are those jobs?We are analyzing data from an initial clinical study. It is a very prevalent and terrible disease. My mother died of osteoporosis. She was 93 years old and was able to play a three-hour concerto from memory, but there came a time when she could not move due to a serious vertebral fracture; She ended up dying from a lung complication. I’m convinced that mesenchymal stem cells may be the solution. We have to carry out the studies to guarantee the safety of this therapy and I cannot yet comment on the results of the trial that we are carrying out at the University of Murcia and the Virgen de la Arrixaca University Hospital, with the group of Jos Mara Moraledabut I can say that the data is promising.What effect do you hope to achieve with that type of cells?Every tissue in the human body has enough mesenchymal stem cells (MSCs) to drive regeneration. But as you age, they are lost and so is that ability to repair tissues. It is something visible on the skin of the young and the old, without going any further. The CMMs exhibit, on the one hand, a anti-inflammatory effectand, on the other hand, they are capable of stimulate the cell of the tissue in which they are found. Because of this regenerative potential, in the future I see young people saving their MSCs to use them as regenerators in old age. They are a fountain of youth.Returning to osteoporosis, what would the cell therapy that you propose consist of? How do they get the mesenchymal cell to go to the damaged bone tissue? The first barrier in regenerative medicine is getting the cells to the place you want to heal. That is the first thing you have to think about or, at least, it is my way of working, I have to know how the treatment I use works, that is why I investigated the mechanisms of cell migration in bone marrow transplantation, and thus I found a important protein in this process, which is Eselectin. Over time I developed a fucosylation technology which allows us to also direct mesenchymal stem cells. Just as leukocytes go to the place in the body where there is an infection or a wound in a matter of seconds, Using blood vessels as a highway, this technology allows MSCs to know where to go, in this case, to the damaged bone tissue. To do this, once extracted from the patients, we expand them and modify the cell membrane, through fucosylation, to install the ‘GPS’ that facilitates their arrival to the bone. It is a technique that we perform through a biochemical reaction in the laboratory.In what other diseases do you think it could be useful?In systemic inflammatory diseases, such as Crohn’s disease, ulcerative colitis, idiopathic pulmonary fibrosis, and also in multiple sclerosis, amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease. MSCs are immunomodulatory cells, which means they reduce inflammation wherever they reach. My idea is that all diseases of old age, degenerative diseases, are caused by a lack of MSC activity in the tissues. I believe in the potential of increase MSC density in places damaged by chronic inflammation.The path of somatic cell therapy, like the one you are investigating, seems more arduous than that of other advanced therapies such as CAR-T immunotherapy or gene therapy, which have already taken off in various diseases. When do you think you will be able to have results with cell therapy?What stops us is the lack of financing, because carrying out a clinical study is very expensive. There is no private interest in promoting this research, which would mean ending the need for chronic treatments for many patients. We make a academic research that seeks healing. If more efforts were added, we could prove our hypothesis in months.
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