Development of a Novel Model to Study Bi-directional Niche Interactions in Skeletal Muscle

Xu, Bella 1, 2 ;  Bakooshli, Mohsen Afshar 2 ;  McGuigan, Alison P. 1, 2 ;  Gilbert, Penney M. 2, 3, 4

1. Department of Chemical Engineering and Applied Chemistry, University of Toronto; 2. Institute of Biomaterials and Biomedical Engineering, University of Toronto; 3. Department of Biochemistry, University of Toronto; 4. Terrence Donnelly Centre for Cellular and Biomolecular Research, Toronto

In acute skeletal muscle loss like trauma caused by surgery, accidents or recovery from medical conditions involving secondary loss of muscle mass, a complete functional recovery is unlikely to be achieved by innate repair. The interactions between muscle regeneration and inflammation have been assumed for decades, and recently the surprising level of coordination between them has been revealed. However, understanding spatial and temporal links between immune system before and after muscle injury is limited by the lack of effective models to recapitulate complicated muscle environment in vitro, while enabling simple stratification and acquisition of data from different cell populations. Here, we describe an engineered model Tissue Roll for Analysis of Cellular Environment and Response (TRACER) that provides a simple strategy to control culture heterogeneity, but simultaneously preserves complex cell-cell interplay that is not possible in traditional co-culture system. Importantly, spatially distinct cell populations can be easily and rapidly isolated on demand for analysis. TRACER has enabled recapitulation of spatial aspects of tumor organization in vivo. Now, TRACER is validated to mimic muscle niche interactions based on known knowledge, and then explore bidirectional signaling between muscle progenitors and immune system during muscle tissue maintenance and repair. Identifying the role of inflammation in skeletal muscle tissue will provide new therapeutic targets to improve muscle growth or regeneration following injury.