Mechanosensory Pathways in Angiocrine Mediated Tissue Regeneration - Mechanical and Chemical Signaling in Angiogenesis - page 18

Mechanosensory Pathways in Angiocrine
Mediated Tissue Regeneration

Sina Y. Rabbany, Bi-Sen Ding, Clemence Larroche
and Shahin Rafii

Abstract Endothelial cells not only form the vascular networks that deliver
nutrients and oxygen throughout the body, they also establish instructive niches
that stimulate organ regeneration through elaboration of paracrine trophogens.
Priming of the vascular niche promotes repair and regeneration of damaged tissues
by establishing an inductive vascular network that temporally precedes new tissue
formation. This induction of endothelial cells provides a platform for essential
instructive cues. Tissue regeneration in certain organs such as the liver, involves
cell mitosis and expansion, which is orchestrated by a dynamic interplay between
cytokines, growth factors, and metabolic pathways. Although the intrinsic events
of cell mitosis have been thoroughly studied, the extrinsic triggers for initiation
and termination of liver regeneration, especially the set points rendered by the
original liver size, are unknown. Furthermore, the gatekeepers that control organ
size remain unidentified. The prevailing dogma states that liver regeneration
involves the proliferation of parenchymal hepatocytes and nonparenchymal cells
such as biliary epithelial cells. However, recent findings also implicate hepatic
sinusoidal endothelial cells (SECs) as drivers of this process. In the classic liver
regeneration model, in which 70 % partial hepatectomy induces regeneration, the
abrupt increase in blood flow into the sinusoidal vasculature of the liver's
remaining lobes correlates with initiation of the regeneration cascade. As such, the
shear stress and mechanical stretch exerted on the endothelial cells may activate
mechanosensory mediated molecular programs, and may be involved in the
elaboration

of endothelial cell-derived angiocrine growth cues that support

S. Y. Rabbany ( & ) B.-S. Ding C. Larroche S. Rafii
Department of Genetic Medicine, Weill Cornell Medical College,
New York, NY 10065, USA
e-mail: [e-mail]
S. Y. Rabbany
Bioengineering Program, Hofstra University, Hempstead, NY 11549, USA