Abstract
Two-photon microscopy has enabled the study of individual cell behavior in live animals. Many organs and tissues cannot be studied, especially longitudinally, because they are located too deep, behind bony structures or too close to the lung and heart. Here we report a novel mouse model that allows long-term single cell imaging of many organs. A wide variety of live tissues were successfully engrafted in the pinna of the mouse ear. Many of these engrafted tissues maintained the normal tissue histology. Using the heart and thymus as models, we further demonstrated that the engrafted tissues functioned as would be expected. Combining two-photon microscopy with fluorescent tracers, we successfully visualized the engrafted tissues at the single cell level in live mice over several months. Four dimensional (three-dimensional (3D) plus time) information of individual cells was obtained from this imaging. This model makes long-term high resolution 4D imaging of multiple organs possible.
Highlights
The use of microscopy in medicine has revolutionized medical research, diagnosis, and treatment [1]
We demonstrated that a wide variety of adult and fetal live tissues could be engrafted into the pinna of the ear
To test whether different tissues can engraft in mouse ear pinna, we transplanted a variety of tissues and pieces of organs including aorta, kidney, bone marrow, spleen, lymph node, skeletal muscle, adrenal gland, ovary, lung, trachea, and thyroid gland from adult B6 CD45.1 mice into the pinnae of the ear in syngeneic recipients
Summary
The use of microscopy in medicine has revolutionized medical research, diagnosis, and treatment [1]. The introduction of newer technologies into microscopes, such as confocal and multiphoton excitation laser scanning microscopy, has enabled study of three dimensional structures deep in living tissues [2]. These technologies have allowed imaging of cells and cellular interactions with high resolution in their intact environments. Surgical exposure allows for only limited visualization in time since multiple surgeries would be required in the same area to allow continued visualization over many weeks. This requirement significantly limits the ability to investigate three dimensional structures over time. There is no viable 3 dimensional microscopic approach to the study of internal human living tissues/organs [3]
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