In our body, we have natural allies against inflammation caused by SARS-CoV-2: we’re talking about stem cells. However, how can they be used to treat COVID-19 patients?
Dr. Giovanna D’Amico, Biologist and expert in Immunology, specialized in Biotechnological Applications and with a European Masters in Immunology, she explains all of this to us. She is currently in charge of the Immunology and Cell Therapy Unit at the Tettamanti Research Center in Monza (Italy). In this article, she will tell us about some specific stem cells called mesenchymal stromal cells — and their anti-inflammatory function for the treatment of patients with SARS-CoV-2 pneumonia.
THE RESCAT STUDY IS THE FIRST IN ITALY IN WHICH MESENCHYMAL CELLS ARE USED ON SARS-COV-2 PATIENTS.
We’ve already spoken about mesenchymal stem cell-based therapies against Coronavirus in an interview with Dr. Giuseppe Astori, and we’ve also addressed the subject of using Artificial Intelligence for data analysis within the AIforCovid project.
But back to Dr. D’amico, so let’s start with some questions to become more familiar with her work and experience.
Dr. D’amico, can you explain to us the importance of mesenchymal stromal cells and their use as a treatment for patients with Coronavirus pneumonia?
“Let’s start by saying that before we got to our current results, the Tettamanti Research Center had been already working on mesenchymal stromal cells for about ten years, with the goal of counteracting Graft versus Host Disease (GvHD). So we have very extensive experience with the anti-inflammatory function of mesenchymal stromal cells. So, when it became clear that one of the major complications relating to COVID-19 was the huge inflammatory response; the so-called cytokine storm, it immediately occurred to us that we could use mesenchymal stromal cells to turn off the inflammation, as we had done with GvHD. Subsequently, the RESCAT multicenter study was born.”
What does the RESCAT project consist of?
“This is a study coordinated by the Azienda Ospedaliero-Universitaria di Modena with the University of Modena and Reggio Emilia. Participating in this study are the Meyer and Careggi Hospitals of Florence, the Policlinico Irccs Ca’ Granda of Milan with the COVID Hospital of Milano Fiera, the San Gerardo Hospital of Monza with the Tettamanti Research Center and with the Milano-Bicocca University, the Azienda Ospedaliera Universitaria Integrata of Verona, and the Azienda Ospedaliera of Vicenza. The Mario Negri Institute of Milan and the Tettamanti Research Center will support the centers in the analysis of biomarkers.
When we started working on this study, there was only one other study performed (by Chinese researchers). We therefore collected the necessary documentation that we then submitted to the AIFA and the Ethics Committee, and a short time ago we received approval to start with the study in actual patients.
In greater detail, the multicenter RESCAT study is a prospective randomized Phase I and IIa study, that is run in order to understand the feasibility and safety of a treatment. It will be comprised of 40 patients who will be treated with mesenchymal stromal cells and 20 patients who will not be treated, and therefore constitute the control group. All patients enrolled in the study will have severe pneumonia from SARS-CoV-2 infection and be admitted to the COVID Units involved in the work.”
What are the advantages and novelties of the RESCAT study?
“First of all, this is the first study in Italy in which mesenchymal cells are used on patients affected by SARS-CoV-2. From other preliminary studies conducted in China and other parts of the world, it appears that the treatment with mesenchymal cells improves oxygenation, determines a decrease in the levels of inflammatory molecules and an improvement in the clinical and radiological image. In addition, no allergic reactions have ever been reported, thus demonstrating the safety of this treatment.
The most important thing about this study is that mesenchymal stromal cells come from different sources: from bone marrow, umbilical cord and adipose tissue.
In addition, they’re allogeneic cells; meaning that they don’t come from the patient, but also meaning that the donor can be basically anyone, so no compatibility is required as with transplants. There is no risk of rejection.
Other important features of the multicenter study are the following:Â
- Reproducibility (i.e. that the treatment works in different laboratories and with different operators). This is a very important feature to be able to adopt it on a large scale
- Ease of enrolling patients by having many COVID Units
- Representativeness of the entire Italian population
- Patients enrolled should not be affected by co-morbidities, in order to evaluate the efficacy of the treatment without the interference of other diseases”.
Can mesenchymal cell treatment only be therapeutic or can it also be preventive?
“Mesenchymal stromal cells, in order to do the required work; that is, to reduce the inflammatory response, must find an inflammatory microenvironment, so they can’t be used in a preventive form but only therapeutic.
However, even if their function is exclusively therapeutic, the effects can potentially be very important and are mainly the following:
- Reduction of the period of hospitalization
- Decrease in oxygenation dependence
- Possible reduction of damage caused by fibrosis with improvement of respiratory efficiency”.
How developed is cell therapy in Italy and what future do you see for its use?
“There’s been considerable progress in the creation of ‘Cell Factories’, such as the one we have at the Tettamanti Foundation and which has been active since 2007, there are now about twenty across Italy. In addition, there’s increasing belief in the use of cells as drugs and consequently in cell therapies. Until recently, the concept of a drug was linked to a chemical compound produced exclusively in industrial laboratories; now, it’s understood that even cells, properly treated, can be used as real drugs.
I hope that there will be further advances in the knowledge and use of cell therapies in various fields, particularly in cancer treatment and not only in leukemias but also in solid tumors.”
Immunology is a very fashionable field these days; however, your interest began some time ago. Can you explain what the spark was that ignited the fire of research within you?
“Since I was a little girl I’ve always shown a great interest in science. A short time ago, I found some drawings that I did as a child that portrayed me with a witch’s hat, while I was looking through a microscope, and then I ran to my mother and said: ‘I’ve found the cure for cancer!’
I developed all my studies in the scientific field, and that spark ignited as a child was fueled when, during the fourth year of high school, I was given the opportunity to do a one-month internship at the Mario Negri Institute, in the Immunology Laboratory of Professor Alberto Mantovani. Then, I enrolled in Biology and when it came to choosing where to go to do my thesis, I returned to the Immunology Lab with the dream of becoming a researcher.”
Tell us about your experience at the Tettamanti Research Center.
“I then had the opportunity to expand my knowledge in the cellular field by moving to Monza; right in the Laboratory of Dr. Biondi’s Tettamanti Research Center. The experience at this new Laboratory has changed my entire approach to research. At the Mario Negri Institute, we did pure research; that is, we manipulated samples that didn’t have a name and therefore couldn’t be traced back to a specific person.
In the Tettamanti Research Center, I started to do applied research, working on samples from children with leukemia (the Research Center is, in fact, part of the Pediatric Clinic of the Maria Letizia Verga Center, where children with leukemia are treated). My passion has changed from wanting to discover something and publish it to trying to help a person, in this case a child who is undergoing chemotherapy upstairs from the Lab. It was a new situation to which I adapted immediately and which also involved me emotionally, prompting me to take an interest in studying the child’s illness.”
After so many years of research, what motivates you to go to the Lab every morning?
“Definitely the desire to be able to find a cure for all children with Acute Lymphoblastic Leukemia (ALL). This is the goal shared with all my collaborators and all the researchers of the Tettamanti Foundation.
Now, as Head of the Lab, I no longer work directly on experiments; however, I supervise the projects of thesis-writing PhD students and the Post Docs. I try to transmit my passion and teach that every result, even negative, is a useful result because it shows us that we’ve taken a wrong path and spurs us to find the right one”.
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