Citations

Abstract The aging immune system responds poorly to infection and vaccination, producing reduced numbers of germinal centers, low affinity antibody titers, and reduced B cell memory. Prolonged contacts between activated B cells and CD4+ T cells are crucial to germinal center formation and T follicular helper cell (Tfh) differentiation, but it is unclear how aging impacts the quality of this interaction. Peptide immunization confirmed that aged mice have less expansion of antigen-specific germinal center B cells and reduced antibody titers. Furthermore, aging was associated with decreased CD4+ T conventional cells and accumulated Tfh cells and regulatory T cells, even in naïve mice. Despite increased numbers, our results indicate that aged Tfh have decreased metabolic function, which may have repercussions on germinal center responses. To determine the contribution of cell-extrinsic influences on antigen-specific Tfh induction, we adoptively transferred young, antigen-specific B and CD4+ naïve T cells into aged hosts prior to peptide immunization, which resulted in reduced antigen-specific germinal center B cell and Tfh expansion and reduced antibody titers when compared to young hosts. The results from these experiments emphasize the importance of the lymphoid microenvironment in germinal center initiation and maintenance. We hypothesize that age-associated Tfh accumulation may impair antigen-specific Tfh induction and subsequent germinal center responses. Current studies use live-cell 2-photon microscopy to track the impact of age on lymphocyte motility and Tfh:B interactions, in order to determine the relative contributions of aged APCs, non-specific aged Tfh, and aged regulatory T cells to germinal center deficiency. Research supported by the Mayo Clinic Robert and Arlene Kogod Center on Aging Innovation Award UL1R002377

AbstractPelvic organ prolapse (POP) is a dysfunction that affects a large proportion of women. Current support scaffolds’ lack of biocompatibility, biodegradability, and mechanical compliance are associated with surgical complications including erosion and pain, indicating the urgent need for new tissue scaffolds with customizable functions. A new material that uses polyvinyl alcohol (PVA) as the main ingredient and is chemically tuned to possess suitable mechanical properties and degradation rates for the surgical treatment of POP is developed. Specifically, the thiol‐norbornene “click” chemistry enables the sol‐gel transition of the biomaterial under UV‐light without side‐products. Meanwhile, NaOH treatment further toughens the hydrogel with a higher crosslink density. The PVA‐based biocompatible ink can be printed with UV‐facilitated direct ink writing due to the rapidly UV‐initiated chemical crosslink; in situ image analysis and machine learning methods are applied during this procedure to quantify and improve the printing quality. The cell viability results demonstrate the biocompatibility of the POP scaffolds, suggesting the potential for future animal studies and the possibility of clinical research. This study bridges polymer chemistry and manufacturing engineering with a specific tissue engineering application to solve the common disorder of POP, shedding light on individualized medicine and intelligent systems for biomedical engineering.