ReSinAge
Financiado
Regeneration of Sinusoidal niches to preserve hematopoiesis after chemotherapy on Ageing
Cancer is a disease of the elderly and chemotherapy remains the mainstay of treatment. The benefits of chemotherapy include increased overall survival, improvement in quality of life, and palliation of symptoms. However, older pat...
Cancer is a disease of the elderly and chemotherapy remains the mainstay of treatment. The benefits of chemotherapy include increased overall survival, improvement in quality of life, and palliation of symptoms. However, older patients are more susceptible to specific toxicities of chemotherapy, like myelosuppression and life-threatening neutropenia. Among the tissues strongly affected by chemotherapy, the bone marrow sinusoidal endothelial cells constitute the most important supportive niche for aged hematopoietic stem cells function and for myelopoietic recovery in the elderly. Up to now, few data are available about how aged sinusoidal niches regenerate upon chemotherapy damage and whether it is possible to rejuvenate vascular endothelial stem cells and improve the regeneration of the old sinusoidal niche as an effective strategy to improve HSC function and prevent myelosuppression and life-threatening neutropenia in the elderly.Here I hypothesize that the reduced regenerative capacity of aged sinusoidal niches can be improved by rejuvenating vascular endothelial stem cells in vivo via targeting Cdc42 activity and the Notch:Jag2 signaling. The current proposal investigates whether improving the regeneration of the aged sinusoidal niche might represent an important target to enhance the hematopoietic recovery and increase the survival after chemotherapy in the elderly. By combining several ground-breaking approaches ranging from single-cell sequencing, whole-mount bone marrow imaging, deep learning strategies for data analysis and integration, stem cell sorting techniques and specific mouse models, this research project will demonstrate that aging is not irreversible and that targeting the stem cell niche could represent an unprecedented innovative strategy to improve the regenerative capacity not only of hematopoietic stem cells.
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Duración del proyecto: 59 meses
Fecha Inicio: 2021-03-01
Fecha Fin: 2026-02-28
Fecha Fin: 2026-02-28
Línea de financiación: concedida
El organismo FP7 notifico la concesión del proyecto el día 2021-03-01
FP7
No se conoce la línea exacta de financiación, pero conocemos el organismo encargado de la revisión del proyecto.
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
FUNDACIO INSTITUT D?INVESTIGACIO BIOMEDICA DE...
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