Cytoprotection: Immune and Matrix Modulation of Tissue Repair
Abstract
The research program consists of a set of projects addressing two Aims:(1) to develop and evaluate formulations of natural cytokines, ligands, and extracellular matrix (ECM) components to promote regulatory T-cell (Treg) and macrophage persistence and function, further to control inflammation and improve healing, and (2) to incorporate promising strategies from Aim 1 into a therapeutic device (the Cytoprotective Implant, or CI) and test it in an engineered replacement for skeletal muscle (the myobridge, also under development in this program). Toward these objectives, significant progress has been made in the following major areas: (1) Novel hyaluronan (HA) ECM hydrogels have been produced that incorporate a number of molecular species to provide potent signals for induction of Treg persistence and function; (2) Small interfering (si)RNAs introduced into na ve human CD4 T-cells were shown to inhibit expression of target genes predicted to affect the generation or stability of Tregs, or inflammatory Th17 T-cells; (3) Beta-2 integrins were implicated as inhibitors of pro-inflammatory responses in a variety of macrophage populations; (4) Inflammatory cytokine blockade with an interleukin 1-receptor antagonist was shown to blunt inflammatory responses in humans; (5) Supportive ECM scaffolds for the CI were evaluated and a novel approach for local, controlled-release of anti-inflammatory HA was developed; and (6) Design and fabrication processes for the myobridge test-bed have been substantially refined.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 14, 2011
- Accession Number
- ADA609549
Entities
People
- Gerald T. Nepom
- Robert B. Vernon
Organizations
- Benaroya Research Institute