An in vivo model allowing continuous observation of human vascular formation in the same animal over time

Abstract

Angiogenesis contributes to numerous pathological conditions. Understanding the molecular mechanisms of angiogenesis will offer new therapeutic opportunities. Several experimental in vivo models that better represent the pathological conditions have been generated for this purpose in mice, but it is difficult to translate results from mouse to human blood vessels. To understand human vascular biology and translate findings into human research, we need human blood vessel models to replicate human vascular physiology. Here, we show that human tumor tissue transplantation into a cranial window enables engraftment of human blood vessels in mice. An in vivo imaging technique using two-photon microscopy allows continuous observation of human blood vessels until at least 49 days after tumor transplantation. These human blood vessels make connections with mouse blood vessels as shown by the finding that lectin injected into the mouse tail vein reaches the human blood vessels. Finally, this model revealed that formation and/or maintenance of human blood vessels depends on VEGFR2 signaling. This approach represents a useful tool to study molecular mechanisms of human blood vessel formation and to test effects of drugs that target human blood vessels in vivo to show proof of concept in a preclinical model.

Poloxamer 188 Exerts Direct Protective Effects on Mouse Brain Microvascular Endothelial Cells in an In Vitro Traumatic Brain Injury Model

“…Song et al found differences between mouse and human brain vasculature, that might be crucial for drug delivery and disease [70]. Interestingly, emerging approaches to address this limitation include an in vivo human blood vessel transplantation model [71].…”

Brain-derived endothelial cells are neuroprotective in a chronic cerebral hypoperfusion mouse model

“…In vivo visualization of transplanted vessels was performed with a TCS/SP8 confocal microscope (Leica Microsystems, Wetzlar, Germany) equipped with a Chamelon laser (Coherent, Santa Clara, CA, USA) as previously reported 49 . During imaging, an animal’s head was immobilized using a custom-made cranial window holder.…”

Visualizing vasculature and its response to therapy in the tumor microenvironment

“…Furthermore, a recent development involves a flexible and sutureless silicon window that enables visualization of muscle tissue and orthotopic breast cancer 106 . Bone windows have been created for imaging brain tumor vasculature 107 and bone marrow 108 , 109 . The cranial window 107 is mainly used for cerebral vessel imaging while the femur window 110 , 111 is used for bone marrow imaging.…”