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

Periodic Reporting for period 3 - bloodANDbone (Blood and bone – conjoined twins in health and disease: bone marrow analogs for hematological and musculoskeletal diseases)

Reporting period: 2020-05-01 to 2021-10-31

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. While it is well established that HSCs are influenced by the bone marrow in their natural environment including MSCs and their progeny, surprisingly little attention has been paid to the reciprocal relationship. 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. For this purpose we need to understand the early events of disease onset and progression. Due to the limitations of such studies in human beings and animals, we are developing human in vitro models of healthy bone marrow, which can be induced to develop hematological and musculoskeletal diseases with high incidence, namely leukemia, multiple myeloma and bone metastasis. Previously we developed a simplified bone marrow analog that bases on macroporous, cell-laden biomaterials with tunable physical, biochemical and biological properties. This versatility enables us to create biomimetic human in vitro models of the human bone marrow in health and disease, which are ground-breaking in their applicability to investigate how the regenerative balance of bone marrow is maintained in health and disturbed in the different kinds of diseases – a prerequisite to develop novel regenerative treatments – as well as their scalability and thus suitability as in vitro test systems for screening of novel drugs or treatments.
The first half of the project was mainly dedicated to building the technological basis for the analysis of the mutual cellular interactions in in vitro models of the healthy and diseased bone marrow. In this endeavor several new biomaterials and methods were developed, established and optimized. In this way, 3D biomimetic in vitro systems of the bone marrow in health and disease were set up that are currently used to study cell-cell interactions in healthy bone marrow and the changes that occur in response to disease development.
The goal of the project bloodANDbone is to find new ways to help patients suffering from haematological or musculoskeletal diseases by understanding the mutual relationship between the blood- and the bone-forming system during regeneration.
Schematic Summary of the project