Carissa Garrity

UC Davis

“Tissue Engineering of Immuno-Universal Cartilage Implants”

Advanced tissue-engineering (TE) methods allow manufacturing of mechanically robust, biomimetic neo-cartilage from allogeneic cartilage cells (chondrocytes) due to their ease of availability and potential of manufacturing off-the-shelf implants. Despite these advantages, transplantation of isolated allogeneic chondrocytes (cartilage cells) elicits a strong immune reaction. The main molecule responsible for allograft rejection is the major histocompatibility complex class I (MHC I). ß-2 micro globulin (B2M) is a structural component of MHC I conserved across species and individuals. Genetic knockout of B2M would cause loss of MHC expression. Over the years, engineering MHC I null cell lines have been investigated on their efficacy to eliminate the risk of immune rejection while retaining cellular function. With CRISPR technology becoming more accessible, fast, and precise, we propose that MHC I can be knocked out from chondrocytes while retaining cellular function to engineer immuno-universal cartilage constructs. We hypothesize that cartilage manufactured from B2M-I null chondrocytes will have comparable functional properties to native cartilage tissue. The novelty of this proposal could have significant advances in cartilage replacement therapies or related tissue transplants.

ABSTRACT

Our laboratory focuses on manipulating cartilage tissue immunology to better tailor tissue engineered cartilage allografts for transplantation. By doing this, our lab will jump start the process of industrializing cartilage tissue replacements for cartilage degenerative disorders.
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