Abstract-The success of therapeutic vascularization and tissue engineering will rely on our ability to create vascular networks using human cells that can be obtained readily, can be expanded safely ex vivo, and can produce robust vasculogenic activity in vivo. Here we describe the formation of functional microvascular beds in immunodeficient mice by coimplantation of human endothelial and mesenchymal progenitor cells isolated from blood and bone marrow.
This model provides a conceptual framework and a reproducible in vivo system to study unresolved central questions in cancer biology regarding the initiation, reversibility, and molecular regulation of the timing of the angiogenic switch.
We report the synthesis and application of an elastic, wearable crosslinked polymer layer (XPL) that mimics the properties of normal, youthful skin. XPL is made of a tunable polysiloxane-based material that can be engineered with specific elasticity, contractility, adhesion, tensile strength and occlusivity. XPL can be topically applied, rapidly curing at the skin interface without the need for heat-or light-mediated activation. In a pilot human study, we examined the performance of a prototype XPL that has a tensile modulus matching normal skin responses at low strain (< 40%), and that withstands elongations exceeding 250%, elastically recoiling with minimal strain-energy loss on repeated deformation. The application of XPL to the herniated lower-eyelid fat pads of 12 subjects resulted in an average 2-grade decrease in herniation appearance in a 5-point severity scale. The XPL platform may offer advanced solutions to compromised skin barrier function, pharmaceutical delivery, and wound dressings.
Summary
Solid tumors require new blood vessels for growth and metastasis, yet the biology of tumor-specific endothelial cells is poorly understood. We have isolated tumor endothelial cells from mice which spontaneously develop prostate tumors. Clonal populations of tumor endothelial cells expressed hematopoietic and mesenchymal stem cell markers and differentiated to form cartilage and bone-like tissues. Chondrogenic differentiation was accompanied by an up-regulation of cartilage-specific col 2a1 and sox 9, whereas osteocalcin and the metastasis marker osteopontin were up-regulated during osteogenic differentiation. In human and mouse prostate tumors, ectopic vascular calcification was predominately luminal and co-localized with the endothelial marker CD31. Thus, prostate tumor endothelial cells are atypically multi-potent and can undergo a mesenchymal-like transition.
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