Transplantation of bone marrow derived macrophages reduces markers of neuropathology in an APP/PS1 mouse model

Abstract

Background We investigated early hallmarks of putative therapeutic effects following systemic transplantation of bone marrow derived macrophages (BM-M) in APP/PS1 transgenic mice. Method BM-M were transplanted into the tail vein and the animals analysed 1 month later. Results BM-M transplantation promoted the reduction of the amyloid beta [37-42] plaque number and size in the cortex and hippocampus of the treated mice, but no change in the more heavily modified pyroglutamate amyloid beta E3 plaques. The number of phenotypically ‘small’ microglia increased in the hippocampus. Astrocyte size decreased overall, indicating a reduction of activated astrocytes. Gene expression of interleukin 6 and 10, interferon-gamma, and prostaglandin E receptor 2 was significantly lower in the hippocampus, while interleukin 10 expression was elevated in the cortex of the treated mice. Conclusions BM-M systemically transplanted, promote a decrease in neuroinflammation and a limited reversion of amyloid pathology. This exploratory study may support the potential of BM-M or microglia-like cell therapy and further illuminates the mechanisms of action associated with such transplants.

Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases

“…Therefore, recent attempts employed hematopoietic stem cells mobilized from bone marrow into the peripheral blood for autologous microglia-like cell preparation [ 369 ], using specific antibodies to convert bone marrow cells into trafficking microglia-like cells [ 367 ]. Additionally, the systemic transplantation of bone marrow-derived macrophages reduced neuroinflammation with a limited reversion of Aβ deposition [ 370 ]. In summary, growing evidence of experimental AD studies demonstrates the capacity of bone marrow-derived microglia and macrophages to enter the CNS and to suppress the progression of brain degeneration, which provides a promising therapeutic tool for AD patients [ 8 , 371 ].…”

Erythropoietin signaling in peripheral macrophages is required for systemic β‐amyloid clearance

“…Our results here also uncover a crucial contribution of peripheral tissue resident macrophages to clear Aβ. Accumulated findings have revealed that Aβ clearance in the periphery contributes substantially to reducing Aβ deposition in the brain (Xiang et al , 2015; Jin et al , 2017; Costa‐Marques et al , 2019). Mounting evidence has demonstrated that phagocytosis via monocytes and macrophages is one of the predominant mechanisms of peripheral clearance of cerebral Aβ in AD (Koronyo‐Hamaoui et al , 2020; Li et al , 2020a).…”

Significance of native PLGA nanoparticles in the treatment of Alzheimer's disease pathology

“…Fixed brain sections (20 μm; parietal cortex and cerebellum) from CSF and PLGA-treated 5xFAD and WT mice as well as cultured neurons were incubated overnight at 4 °C with various antibodies (see enclosed Table 1 ) and then processed as for immunostaining as described earlier [ 48 ]. In parallel, brain sections (3–5 sections/mouse) immunostained with anti-Aβ OC antibody were processed to quantify plaque load in both CSF- and PLGA-treated 5xFAD mice (n = 3/group) as described earlier [ 49 ]. Immunostained sections/cells were visualized using a Nikon Eclipse 90i fluorescence microscope with a Retiga 2000R Q imaging system (Nikon Instruments Inc., NY, USA) or with a Zeiss multiphoton confocal laser scanning microscope (LSM700, Carl Zeiss, Inc.).…”