Blood and bone – conjoined twins in health and disease: bone marrow analogs for hematological and musculoskeletal diseases

Informations projet

bloodANDbone

N° de convention de subvention: 757490

DOI

10.3030/757490

Projet clôturé

Date de signature de la CE 6 Novembre 2017

Date de début 1 Février 2018

Date de fin 31 Decembre 2023

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 499 920,00

Contribution de l’UE

€ 1 499 920,00

Coordonné par

GOTTFRIED WILHELM LEIBNIZ UNIVERSITAET HANNOVER
Germany

Periodic Reporting for period 5 - bloodANDbone (Blood and bone – conjoined twins in health and disease: bone marrow analogs for hematological and musculoskeletal diseases)

Période du rapport: 2023-05-01 au 2023-12-31

Résumé du contexte et des objectifs généraux du projet

Blood and bone are closely intertwined. Their intrinsic regenerative capacities are disturbed in many hematological and musculoskeletal diseases. Re-establishing the regenerative potential is the key to cure these diseases by regenerative medicine. Multipotent stem cells of both tissues – hematopoietic stem cells (HSCs) for blood and mesenchymal stem/stromal (MSCs) for bone – are the basis for their regenerative capacity. The hypothesis of the project bloodANDbone is that only when taking both tissues and their mutual crosstalk into account, we will be able to understand how the regenerative potential of blood and bone is impaired in disease and how it can be re-established with novel treatment strategies.
To gain a deep understanding of the mutual interaction between the regenerative systems of blood and bone, we developed in vitro models of the human bone marrow in health and disease with the help of tailor-made biomaterials. These models allowed us to investigate how the regenerative balance of the bone marrow is maintained in health and disturbed in leukemia, multiple myeloma and bone metastasis.
In our studies, MSCs emerged as key regulators in the crosstalk of the bone marrow regenerative systems in health and the studied diseases. Furthermore, we found strong donor dependencies in these mutual relationships highlighting the importance of developing individualized treatment concepts. To address this need, we showed in a proof-of-principle study the possibility to create patient cell-derived in vitro models of bone marrow. These models could be applied e.g. for drug testing in individualized medicine approaches. The results hold significance for the development of future treatments for patients suffering from hematological and musculoskeletal diseases.
In conclusion, our research successfully elucidated fundamental principles and consequences of cellular interactions within the human bone marrow in health and disease, offering insights with implications for both fundamental science and the advancement of regenerative therapies.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

To enable the analysis of the mutual cellular interactions in healthy and diseased bone marrow, several new biomaterials and methods around the intended in vitro models were developed, established and optimized. In this way, 3D biomimetic in vitro systems of the bone marrow in health and disease were set up and applied to study cell-cell interactions in healthy bone marrow and the changes that occur in response to disease development.
The results were patented where applicable, published in peer-reviewed journals and presented at numerous scientific meetings. Further publications are in preparation or currently under review. Furthermore, the public was informed about the conducted research at the institute and applied technologies e.g. during the Science Night 2023 in Hannover.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The goal of the project “bloodANDbone” was to find new ways to help patients suffering from hematological or musculoskeletal diseases by understanding the mutual relationship between the blood- and the bone-forming system during regeneration. We could achieve this goal with the help of in vitro systems, which were based on tailor-made biomaterials. Notably, one of these materials demonstrated superior functionality compared to existing approaches for printing bone tissue. Thus, it appeared promising for bone regeneration and is currently validated for its potential clinical application. Across the spectrum of studied diseases—leukemia, multiple myeloma, and bone metastasis—we demonstrated the significance of intercellular interactions and elucidated the central role of MSCs. Moreover, working with cells from different human donors allowed us to determine the substantial impact of individual differences on the parameters under study, emphasizing the necessity of developing personalized treatment strategies. In addition to answering the question on the significance of the crosstalk of the two regenerative systems in bone marrow from a fundamental science perspective, the developed in vitro models hold promise as test systems for future developments of individualized regenerative treatments.

Schematic Summary of the project