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Engineering an integrated platform for generation of human blood stem cells from pluripotent sources

Project description

Off-the-shelf production of blood stem cells

Allogeneic haematopoietic stem cell (HSC) transplantation relies on matched donors, yet a significant proportion of patients lack a compatible match. Off-the-shelf HSCs derived from pluripotent stem cells could overcome this barrier. However, current in vitro models fail to reliably generate functional HSCs. The ERC-funded MakingBlood project aims to construct a modular platform that recreates the distinct environments HSCs encounter during development. The research team will investigate the cellular context as well as the chemical cues and mechanical properties that drive HSC formation and expansion. By integrating these insights, they aim to engineer a niche that can reliably generate and sustain HSCs in vitro. The ultimate goal is to use this system for on-demand blood production and for reducing dependence on donor-derived transplants.

Objective

Life-saving blood cell replacement depends on voluntary donors. Availability is a challenge for specific groups, and 25% of patients needing blood stem cell transplants lack a compatible donor. The ideal alternative is clinical-scale production of Haematopoietic Stem Cells (HSC) from laboratory-maintained tissue-compatible sources, to provide an off-the-shelf source of blood cells. HSC are generated in the aorta/gonad/mesonephros region of the embryo, expand in the foetal liver, and are maintained in the bone marrow of adults. Current attempts to generate HSC in vitro do not consider the changing cellular, chemical, and physical characteristics of the different environments met by HSC in vivo from embryo to adult, and have been unable to reliably produce functional HSC. MakingBlood aims to establish a proof-of-concept platform for robust generation of human HSC from pluripotent stem cells by developing a self-organising gastruloid model of embryonic HSC generation without genetic manipulation, and successively recapitulating the natural foetal and adult HSC development environments. MakingBlood brings together an expert in HSC embryonic development, a national blood bank research director with expertise in adult HSC, an expert in molecular regulation of cell fate choices, and a bioengineer with expertise in mechanical and chemical integration for tissue production to deliver this breakthrough platform. By using state-of-the-art technology and multidisciplinary approaches, we will systematically detangle cellular, chemical, and physical properties of natural HSC generation, amplification and maintenance microenvironments, and iteratively identify essential elements that enable and promote HSC function. We will integrate key elements into modular scalable engineered niches to establish a HSC production platform, which can be developed as a bioreactor for on-demand blood production, and eventually replace donations as the clinical source of HSC and mature blood cells.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-ERC-SYG - HORIZON ERC Synergy Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2024-SyG

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Host institution

FUNDACIO INSTITUT HOSPITAL DEL MAR D INVESTIGACIONS MEDIQUES
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 076 500,00
Address
Doctor Aiguader 88
08003 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 076 500,00

Beneficiaries (5)

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