Blood stem cells, or hematopoietic stem cells, are located in the bone marrow, a highly dynamic and specialised tissue within the cavity of long bones. They are responsible for the vital function of continuously producing all types of blood cells: red blood cells (oxygen transporters), megakaryocytes (future platelets) and white blood cells (immune cells, lymphocytes and macrophages). Over time, however, stem cells also do age, they lose their regenerative capacity and generate fewer and lower quality immune cells. This has been linked to immunosenescence, chronic low grade inflammation and certain chronic diseases.
In their nucleus, as they replicate, blood stem cells can accumulate mutations and lose epigenetic marks that used to keep DNA well-arranged, ultimately increasing mechanical tension on the nuclear envelope. This study figured out RhoA is a mechanosensor activated by such tension and conducts a key role in the stem cell ageing process. Researchers subsequently proved its rejuvenating potential: after ex vivo treatment of blood stem cells with the drug Rhosin, a RhoA inhibitor, they observed an improvement in aged-related markers. As IDIBELL researcher and study co-author Dr Eva Mejía-Ramírez summarizes: “Overall, our experiments show that Rhosin did rejuvenate blood stem cells, increased the regenerative capacity of the immune system and improved the production of blood cells once transplanted in the bone marrow.” The in vitro and in vitro assays took place in IDIBELL, while Dr Paula Petrone and Pablo Iañez Picazo from ISGlobal and the Barcelona Supercomputing Centre discovered the chromatin remodelling induced by Rhosin using an innovative machine learning approach. This project also relies on a long-term collaboration with Prof. Yi Zheng at CCHMC, who had previously developed the Rhosin molecule.
In 2050 the population over 60 in Western countries will have doubled compared to 2015. This will lead to a higher incidence of many chronic diseases such as cancer, dementia and cardiovascular conditions, placing a major burden on all countries health and social systems. Quality biomedical research becomes indispensable to design treatments that relieve the negative effects of ageing on health, regardless of aesthetic or cosmetic aspects. There is positive scientific evidence on lifestyle changes and some pharmacological treatments that may qualify as anti-ageing, together with some promising research lines that explore the aging phenomena on a molecular level. However, according to Dr. Florian, "These measures cannot be qualified as rejuvenation because they combat the effects of ageing rather than acting on the process itself. In contrast, we target the core of the ageing process: by reverting blood stem cells to a younger state, we make them more capable of regenerating and producing new healthy blood cells, which improves the health of the whole organism. This is why we talk about cell rejuvenation."
Results are promising and researchers feel very optimistic about how this new strategy might improve the quality of life of the elderly. Now, clinical research must verify whether the results in animal models can be safely and effectively translated to humans. In this line, Dr Florian counted on the IDIBELL Innovation Unit to submit the results for a European patent, an essential legal instrument to enable the potential commercialization of this innovative drug and prevent unappropriate use by third parties.
Mejía-Ramírez E, Picazo PI, Walter B, Montserrat-Vazquez S, Affuso F, Wieser S, Pezzano F, Reymond L, Castillo-Robles J, Matteini F, Mularoni L, Maciá D, Raya Á, Ruprecht V, Zheng Y, Petrone P, Florian MC.
Targeting RhoA nuclear mechanoactivity rejuvenates aged hematopoietic stem cells.
Nat Aging. 2025 Nov 24. doi: 10.1038/s43587-025-01014-w