Abstract
The bone marrow is a central organ of the immune system, which hosts complex interactions of bone and immune compartments critical for hematopoiesis, immunological memory, and bone regeneration. Although these processes take place over months, most existing imaging techniques allow us to follow snapshots of only a few hours, at subcellular resolution. Here, we develop a microendoscopic multi-photon imaging approach called LIMB (longitudinal intravital imaging of the bone marrow) to analyze cellular dynamics within the deep marrow. The approach consists of a biocompatible plate surgically fixated to the mouse femur containing a gradient refractive index lens. This microendoscope allows highly resolved imaging, repeatedly at the same regions within marrow tissue, over months. LIMB reveals extensive vascular plasticity during bone healing and steady-state homeostasis. To our knowledge, this vascular plasticity is unique among mammalian tissues, and we expect this insight will decisively change our understanding of essential phenomena occurring within the bone marrow.
Highlights
The bone marrow is a central organ of the immune system, which hosts complex interactions of bone and immune compartments critical for hematopoiesis, immunological memory, and bone regeneration
In order to understand tissue and cellular dynamics in the bone marrow on a longer time scale, we developed a biocompatible implant—the longitudinal intravital imaging of the bone marrow (LIMB) implant, which allows microendoscopic imaging of the femoral bone marrow
While intravital imaging of the bone marrow has previously been performed[3, 11,12,13,14,15,16,17,18, 22], longitudinal multi-photon imaging in the deep marrow of long bones over the time course of months was not feasible
Summary
The bone marrow is a central organ of the immune system, which hosts complex interactions of bone and immune compartments critical for hematopoiesis, immunological memory, and bone regeneration These processes take place over months, most existing imaging techniques allow us to follow snapshots of only a few hours, at subcellular resolution. The approach consists of a biocompatible plate surgically fixated to the mouse femur containing a gradient refractive index lens This microendoscope allows highly resolved imaging, repeatedly at the same regions within marrow tissue, over months. Imaging the bone marrow of long bones is more invasive, as it requires the surgical ablation of cortical bone Both methods have been used mainly as terminal procedures, imaging at multiple time points has been used for intravital microscopy of both calvarium[17, 18] and long bones (femur and tibia) for imaging durations of hours, over a maximum of 40 days[15, 16]. In order to understand the cellular dynamics occurring in those marrow regions over longer periods of time, an intravital imaging approach allowing longitudinal observation of a fixed region within the bone marrow in one and the same subject is needed
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