Innovating Works

HSC-reNEW

Financiado
Dissecting the molecular regulation of hematopoietic stem cell emergence using p...
Dissecting the molecular regulation of hematopoietic stem cell emergence using pluripotent stem cells to improve ex vivo therapies Although hematopoietic stem cell (HSCs) transplantation is routinely used to treat blood disorders, immune incompatibility and donor shortage remain critical clinical barriers. Likewise, since high number of HSCs are needed for su... Although hematopoietic stem cell (HSCs) transplantation is routinely used to treat blood disorders, immune incompatibility and donor shortage remain critical clinical barriers. Likewise, since high number of HSCs are needed for successful transplants, the absence of reliable expansion protocols prevents the wider application of this cell therapy. In fact, while HSC-based gene therapy represents a revolutionary treatment also for novel and unexpected indications, the ex vivo manipulation required for HSCs engineering results in loss of their stemness potential. Patient-specific induced pluripotent stem cells (PSCs) could serve as a solution to these problems, as they would provide a potentially unlimited, easy to engineer, source of immunologically matched HSCs. However, despite recent advances, the robust de novo generation of HSCs remains unrealized due to an incomplete understanding of how HSCs are generated during embryonic development, a process that, as such, cannot be accurately recapitulated in vitro. To tackle these issues, in this proposal we will leverage on our proven expertise in PSC differentiation and hematopoietic development. In particular, we will use innovative in vitro assays and systematic measurements to determine at the molecular level how HSC precursors control their gene expression to generate blood cells (Aim 1). Combining the study of the highly proliferative emerging embryonic HSCs with a CRISPR-based gain-of-function screen, we will uncover the molecular regulators of the extensive embryonic self-renewal, thus enabling robust specification of HSCs from PSCs (Aim 2). We will design strategies to resurrect this embryonic self-renewal program in postnatal HSCs for their in vitro expansion (Aim 3). The successful completion of these studies will accomplish the long-standing goals of generating and expanding HSCs in vitro, allowing the fully exploitation of the transformative therapeutic potential of HSC-based cell and gene therapies. ver más
29/02/2028
OSR
2M€
Perfil tecnológico estimado
Duración del proyecto: 62 meses Fecha Inicio: 2022-12-15
Fecha Fin: 2028-02-29

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-12-15
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2021-COG: ERC CONSOLIDATOR GRANTS
Cerrada hace 3 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
OSPEDALE SAN RAFFAELE SRL No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5