Biomaterials direct functional B cell response in a material-specific manner.

B cells are an adaptive immune target of biomaterials development in vaccine research but, despite their role in wound healing, have not been extensively studied in regenerative medicine. To probe the role of B cells in biomaterial scaffold response, we evaluated the B cell response to biomaterial materials implanted in a muscle wound using a biological extracellular matrix (ECM), as a reference for a naturally derived material, and synthetic polyester polycaprolactone (PCL), as a reference for a synthetic material. In the local muscle tissue, small numbers of B cells are present in response to tissue injury and biomaterial implantation. The ECM materials induced mature B cells in lymph nodes and antigen presentation in the spleen. The synthetic PCL implants resulted in prolonged B cell presence in the wound and induced an antigen-presenting phenotype. In summary, the adaptive B cell immune response to biomaterial induces local, regional, and systemic immunological changes.

The Immune System and Its Contribution to Variability in Regenerative Medicine.

The immune system plays a critical role in directing tissue repair and regeneration outcomes. Tissue engineering technologies that are designed to promote new tissue growth will therefore be impacted by immune factors that are present in patients both locally at the site of intervention and systemically. The immune state of patients can be influenced by many factors, including infection, nutrition, and other disease comorbidities. As a result, the immune state is highly variable and may be a source of variability in tissue-engineered products in the clinic, which is not found in preclinical models. In this review, we will summarize key immune cells and evidence of their activity in tissue repair and potential in tissue engineering systems. We also discuss how clinical translation of tissue engineering strategies, in particular stem cells, helped elucidate the importance of the immune system. With increased understanding of the immune system's role in repair and tissue engineering systems, it will likely become a therapeutic target and component of future therapies.

Landscape of transcript isoforms in single T cells infiltrating in non-small-cell lung cancer.

Single-cell RNA sequencing (scRNA-seq) has enabled high-resolution characterization of molecular signatures of tumor-infiltrating lymphocytes. However, analyses at the transcript isoform level are rarely reported. As alternative splicing is critical to T-cell differentiation and activation, here, we proposed a computational method named IDEA (Isoform Detection, Enrichment, and functional Annotation) to comprehensively detect and annotate differentially used isoforms across cell subtypes. We applied IDEA on a scRNA-seq data set of 12,346 T cells from non-small-cell lung cancer (NSCLC). We found that most genes tend to dominantly express one isoform in single T cells, enabling typing T cells based on the isotypes, given a gene. Isotype analysis suggested that tumor-infiltrating T cells significantly preferred specific isotypes for 245 genes in CD8+ T cells and 456 genes in CD4+ T cells. Functional annotation suggests that the preferred isoforms involved in coding/noncoding switches, transcription start site changes, gains/losses of domains, and subcellular translocation. Clonal analysis revealed that isoform switching occurred during T-cell activation/differentiation. Our analysis provides precise characterization of the molecular events in tumor-infiltrating T cells and sheds new light on the regulatory mechanisms of tumor-infiltrating T cells.