Mechanosensory Pathways in Angiocrine Mediated Tissue Regeneration

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

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

2 Scopus citations

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 hepatocyte proliferation. Physiological liver regeneration would therefore depend on the proper inductive and proliferative functioning of liver SECs. Thus, uncovering the cellular mechanisms by which organisms recognize and respond to tissue damage remains an important step towards developing therapeutic strategies to promote organ regeneration. In this chapter, we demonstrate the mechanism by which tissue-specific subsets of endothelial cells promote organ regeneration, and further discuss the roles of physical forces and molecular signals in initiating and terminating angiocrine-mediated tissue regeneration.

Original languageEnglish
Title of host publicationStudies in Mechanobiology, Tissue Engineering and Biomaterials
PublisherSpringer
Pages19-45
Number of pages27
DOIs
StatePublished - 2013
Externally publishedYes

Publication series

NameStudies in Mechanobiology, Tissue Engineering and Biomaterials
Volume12
ISSN (Print)1868-2006
ISSN (Electronic)1868-2014

Keywords

  • Hepatocyte Growth Factor
  • Liver Regeneration
  • Partial Hepatectomy
  • Portal Blood Flow
  • Vascular Endothelial Growth Factor

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