Hematopoietic stem cell transplantation and its influence on the bone structure and marrow cells

Background

In most malignant hematological diseases the preferential treatment is a hematopoietic stem cell transplantation (HSCT). Initially, lymphopenia and diminished immunity is associated with HSCT. Several studies proved a higher risk of fractures and osteoporosis after HSCT. However it is rarely studied what happens on the cellular level within the bone directly after transplantation. This project aims to investigate the underlying proceedings responsible for changes in the bone after HSCT.

Methods

Within our group, a mouse model for HSCT has been developed to investigate bone and changes within during graft versus host disease (GVHD). Two groups were investigated a) syn = control without GVHD after HSCT and b) allo = a group that developed acute GVHD. 20, 40 and 60 days after cell transfer animals were sacrificed and bones were harvested. Bones underwent radiological and histological analyses. Consecutively, primary human mesenchymal stromal cells and osteoblasts were stimulated to differentiate and analyzed with metabolic assays and specific stainings in a GVHD simulating in vitro setting. During this stimulation, media immunized with immune cells were added to examine their potential to influence bone homeostasis.

Results

Femora of mice developing a strong GVHD after allogeneic transplantation showed a larger medullary area and thinner cortical bone in the diaphyseal as well as an increase in bone volume and trabecular number in the epiphyseal region revealing differences in the whole bone structure. Also, no osteoblastic lining cells were detectable and osteoid formation was absent, indicating an impaired bone formation capacity due to the GVHD. Furthermore, deviating B cell numbers and distributions were seen. The in vitro analyses demonstrated the involvement of immune cell signaling seen in impaired – T cells or improved – B cells osteogenesis.

Conclusion

Impaired recovery of the immune system after allogeneic HSCT not only leads to an increased risk of severe infections. By examining bone structure and stroma cells we could prove that the imbalance of immune cells of the adaptive immune system impedes the bone structure. This is caused by a decreased capacity of osteogenic differentiation due to the lack of B cells. This discovery may be significant for the prognosis and treatment of long-term effects on the musculoskeletal tissue after HSCT.

Offenlegung Interessenkonflikt:

No conflict of interest is present in this project.