Edward A. Botchwey, III, PhD
Edward A. Botchwey, III, Ph.D.
Associate Chair for Undergraduate Studies
Wallace H. Coulter Dept. of Biomedical Engineering
Endothelial cells play significant roles in conditioning the environment in local tissues after injury by the production and secretion of angiocrine factors. At least two distinct subsets of monocytes, CD45+CD11b+Ly6C+Gr1+CX3CR1lo inflammatory and CD45+CD11b+Ly6CGr1-CX3CR1hi anti-inflammatory monocytes, respond differentially to these angiocrine factors and promote pathogen/debris clearance and arteriogenesis/tissue regeneration, respectively. We demonstrate here that local sphingosine 1-phosphate receptor 3 (S1P3) agonism recruits anti-inflammatory monocytes to remodeling vessels. Poly (lactic-co-glycolic acid) thin films were used to deliver FTY720, a S1P1/3 agonist, to inflamed and ischemic tissues, which resulted in a reduction in pro-inflammatory cytokine secretion and an increase in regenerative cytokine secretion. The altered balance of cytokine secretion results in a reduction in inflammatory monocyte recruitment and an increase in anti-inflammatory monocyte (CX3CR1hi) recruitment to a perivascular niche. The chemotaxis of these cells, which express more S1P3 than inflammatory monocytes, towards SDF-1α was also enhanced with FTY720 treatment. FTY720 delivery enhanced arteriolar diameter expansion and increased length density of the local vasculature: classic signs of vascular remodeling. This work establishes a role for S1P receptor signaling in the local conditioning of tissues by angiocrine factors that preferentially recruit regenerative monocytes that can enhance healing outcomes, tissue regeneration, and biomaterial implant functionality.
The Botchwey Laboratory takes a multidisciplinary approach for improvement of tissue engineering therapies through study of microvascular remodeling, inflammation resolution and host stem cells. Our goal is development of effective new strategies to repair, replace, preserve or enhance tissue or organ function. We are located in the The Parker H. Petit Institute for Bioengineering and Bioscience (IBB) at Georgia Tech.