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.
