As a student at Harvard University, Robert Sackstein began to have contact with bone marrow transplants; He then found that one in four patients receiving the treatment died shortly after graft failure: the transplanted cells could not find their way through the bloodstream to the bone marrow.

So he began to delve into the molecular mechanisms that guide cells in this process, for which he had the help as a mentor of the Nobel Prize in Medicine and pioneer in the development of transplantation Donnall Thomas. Sackstein's research has culminated in a technology based on the modification of cell membranes by inserting 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 very young. Despite the vicissitudes of his childhood and youth, or perhaps thanks to them, he never abandoned an early fixation on treating the disease but "always understanding how". Now professor emeritus at Harvard and vice president for medical affairs at Florida International University in Miami, Sackstein is proud of the influence of his Cuban family, with Spanish ancestry, in this interview with him in Los Alcázares. Here he has co-directed a course on Advanced Therapies organized by the Spanish Society of Hematology and Hemotherapy (SEHH), the Carlos III Health Institute and the University of Murcia.

No one would assume from his name that he has a Leonese 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 U.S. Army in World War II, and 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 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 surname 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. He went to Cuba at the age of 20 and never returned to Spain, but he always had it very present; He told us many anecdotes of his hometown and I grew up knowing him very well. So much so, that a few years ago I went to see the town and it was as it was described to me. Is it true that his 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 military veterans. In 1960, they shot the president of that organization, a good friend of my family, and warned my mother that my father would be next. Che Guevara himself wanted to shoot him. It was to know it and flee to Miami with a suitcase. I was three years old about to turn four. Even though my parents told me we were going on vacation, I remember my mother crying a lot. He didn't understand his sadness. I see it as if it were yesterday. A few years ago, I met again with one of my neighbors at the time 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 after them. Already exiled in Miami, you were a very precocious child; it was immediately clear to you that you wanted to be a doctor.When we arrived we lived 19 people in a three-room house. My grandmother always went to sleep at 3 o'clock in the afternoon for a while, because her head hurt a lot, and I thought it was because of the war I gave him, because he was a very busy child. Then we learned he had high blood pressure. There were very few treatments then and I promised him that I would find him one. That's how at age 12 I started going to the University of Miami library to study the disease. At the time, a hypertension expert, Professor Murray Epstein, was doing research at that university. I asked my father to help me get to know him and we got an appointment with one of his assistants. I remember that he was very surprised to see me, because he did not imagine that I was a 13-year-old boy. They couldn't offer me a job for someone my age in the lab, but my father insisted, "My son knows how to work hard." And they let me volunteer. I was in charge of cleaning the boxes of the rats of the experiments. He cleaned them thoroughly, with a toothbrush. He left them so clean, that the data collected were free of any contaminating element and the experiments advanced very quickly. Soon they were in a position to start theClinical trial with the drug, which turned out to be captopril. As a thank you for the effort, I was allowed to include my grandmother in the study. Then I knew I wanted to be a doctor, but also work in the lab. That determination in such a young person is striking. Did it have any influence on your family?An uncle of mine was a surgeon, but what I wanted was to heal as a researcher, to do science. My mother taught us music; I soon saw that it was not my thing, unlike what happened to my sister, who was very talented. On the other hand, I had much more facilities for science. Also, when I was little I was shocked 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. Of course he has fulfilled it, because throughout his career he has always combined the clinic with research. He is now focused on developing a somatic cell therapy to treat osteoporosis. Where are these jobs?We are analyzing data from an initial clinical trial. It is a very prevalent and terrible disease. My mother died of osteoporosis. He was 93 years old and able to play a three-hour concert from memory, but there came a time when he could not move because of a serious vertebral fracture; He ended up dying from a pulmonary complication. I am convinced that mesenchymal stem cells may be the solution. We have to do the studies that guarantee the safety of this therapy and I still cannot comment on the results of the trial we are carrying out at the University of Murcia and the Virgen de la Arrixaca University Hospital, with the group of José María Moraleda, but I can say that the data are promising. What effect do you hope to achieve with these types of cells?Every tissue in the human body has enough mesenchymal stem cells (MSCs) to drive regeneration. But as you age, you lose and so does that ability to repair tissues. It is something visible on the skin of young and old, without going any further. MSCs exhibit, on the one hand, an anti-inflammatory effect, and, on the other, they are able to stimulate the cell of the tissue in which they are located. Because of this regenerative potential, in the future I see young people saving their MSCs to use as regenerators in old age. They are a fountain of youth. Returning to osteoporosis, what would the cell therapy 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 to think or, at least, it is my way of working, I have to know how the treatment I use works, so I investigated the mechanisms of cell migration in bone marrow transplantation, and so I found an important protein in that process that is Eselectin. Over time I developed a fucosylation technology that allows us to target mesenchymal stem cells as well. 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 us to MSCs know where to turn, in this case, to 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 at the bone. It is a technique that we perform through a biochemical reaction in the laboratory. What other diseases do you think it might be helpful in?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 go. My idea is that all diseases of old age, degenerative diseases, are caused by the lack of activity of MSC in the tissues. I believe in the potential to increase the density of MSC in places damaged by chronic inflammation.The path of somatic cell therapy, such as 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 they might have results with cell therapy?What holds us back is the lack of funding, because conducting a clinical trial 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 do academic research that seeks healing. If more efforts were added, we could prove our hypothesis in months.

  • Longevity
  • Advanced therapies