A discovery on the mechanisms underlying the laboratory generation of stem cells opens new perspectives for the treatment of blood diseases: Identification of a Retinoic Acid-Dependent Haemogenic Endothelial Progenitor from Human Pluripotent Stem Cells is the medical sciences study that has won the eleventh edition of the Aspen Institute Italia Award for Scientific Collaboration and Research between Italy and the United States.
Blood stem cell transplantation, more commonly known as bone marrow transplantation, is today one of the most established examples of regenerative medicine, used to regenerate healthy tissues and replace those damaged in a wide range of diseases, including immunodeficiencies and leukemias. Despite their widespread clinical use, blood stem cells remain highly complex to study: they are rare, difficult to identify with precision and, in adult life, exist in a quiescent state, becoming active only in response to specific physiological demands.
For these reasons, although it is possible to isolate blood stem cells and genetically modify them, we are still not able to produce them efficiently in the laboratory. The ability to generate them in large quantities would have extraordinary implications, as it would enable both the development of large-scale therapies without recurring to bone marrow donors and a more precise understanding of immune system development and the origin of genetic blood disorders. However, the complete “recipe” to generate blood stem cells in vitro has not yet been fully defined.
In this context, the collaboration between the laboratory of Andrea Ditadi at the San Raffaele Telethon Institute for Gene Therapy and the laboratory of Christopher Sturgeon at the Black Family Stem Cell Institute at Mount Sinai Hospital in New York has provided a key advance. The study identified the role of retinoic acid, also known as vitamin A, in guiding the generation of blood stem cells.
This discovery emerged from the comparison of independent yet complementary observations made in the two laboratories, among the few worldwide carrying out this type of research. The results, like pieces of a puzzle, made it possible to pinpoint with precision the exact timing at which this signal, retinoic acid, must be introduced to promote the formation of blood stem cells in vitro.
These findings have defined the conditions required for the generation of blood stem cells in the laboratory, an objective long considered one of the major goals of regenerative medicine. Although the process still requires optimization to improve its efficiency, the path forward is now clearly outlined.
The research is now focused on refining this system, increasing its yield and understanding the mechanisms that are altered in genetic blood diseases. In this effort, the collaboration between Italy and the United States continues in a close and sustained manner, through an open exchange of ideas, data and expertise. This collaborative model represents a key element in addressing complex scientific challenges and in driving innovation with tangible impact on human health.
The awarded study (published in 2022 in Nature Cell Biology, Vol. 24, pp. 616–624) was carried out through the collaboration of thirteen scientists:
- Andrea Ditadi
- Sara Valsoni
- Rebecca Scarfò
- Sara Cascione
- Lauren N. Randolph
- Eleonora Cavalca
San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan
- Ivan Merelli
San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan
Institute for Biomedical Technologies, National Research Council – CNR
- Christopher M. Sturgeon
- Stephanie A. Luff
Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY
Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY
Department of Medicine, Division of Hematology, Washington University School of Medicine, St. Louis, MO
- J. Philip Creamer
- Carissa Dege
Department of Medicine, Division of Hematology, Washington University School of Medicine, St. Louis, MO
- Analisa Dacunto
Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY
Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY
- Samantha A. Morris
Department of Developmental Biology, Washington University in Saint Louis, St. Louis, MO
Department of Genetics, Washington University in Saint Louis, St. Louis, MO
THE AWARD
The Aspen Institute Italia Award for scientific research and cooperation between Italy and the United States, established in December 2015 in the context of the Institute’s unflagging commitment to the internationalization of leadership and to transatlantic relations, celebrates this year its eleventh edition. The Award is assigned each year to research in the field of natural, theoretical or applied science that is the product of collaboration between scientists and/or research organizations in Italy and in the United States.
The Award is designed to consolidate the Institute’s commitment to organizing initiatives and in-depth discussions on issues associated with scientific culture and technological innovation, with a special focus on their relevance to Italy. The panel of judges, chaired by Hon. Prof. Giulio Tremonti, President of Aspen Institute Italia, is composed of:
- Prof. Cristina M. Alberini, Center for Neural Science, New York University, New York
- Prof. Alessandra Buonanno, Director, Max Planck Institute for Gravitational Physics – Albert Einstein Institute, Potsdam
- Prof. Domenico Giardini, Chair of Seismology and Geodynamics, ETH, Zurich
- Prof. Luciano Maiani, Professor Emeritus of Theoretical Physics, Sapienza University of Rome
- Prof. Giovanni Rezza, Associate Professor of Hygiene, Università Vita-Salute San Raffaele, Milan
- Dr. Lucio Stanca, Vice President, Aspen Institute Italia, Rome