COVID-19 infection and vaccination rarely impact HLA antibody profile in waitlisted renal transplant candidates- a multicenter cohort

Although rare, infection and vaccination can result in antibodies to human leukocyte antigens (HLA). We analyzed the effect of SARS-CoV-2 infection or vaccination on HLA antibodies in waitlisted renal transplant candidates. Specificities were collected and adjudicated if the calculated panel reactive antibodies (cPRA) changed after exposure. Of 409 patients, 285 (69.7 %) had an initial cPRA of 0 %, and 56 (13.7 %) had an initial cPRA > 80 %. The cPRA changed in 26 patients (6.4 %), 16 (3.9 %) increased, and 10 (2.4 %) decreased. Based on cPRA adjudication, cPRA differences generally resulted from a small number of specificities with subtle fluctuations around the borderline of the participating centers’ cutoff for unacceptable antigen listing. All five COVID recovered patients with an increased cPRA were female (p = 0.02). In summary, exposure to this virus or vaccine does not increase HLA antibody specificities and their MFI in approximately 99 % of cases and 97 % of sensitized patients. These results have implications for virtual crossmatching at the time of organ offer after SARS-CoV-2 infection or vaccination, and these events of unclear clinical significance should not influence vaccination programs.     

Poly(acrylamide) Spheroids with Tunable Elasticity for Scalable Cell Culture Applications

Many biological tissues resemble hydrogels and display Young's moduli below 50 kPa, corresponding to most cell types for the natural environmental conditions to grow. Contrastingly, conventional cell culture usually involves rigid substrates resulting in stiff priming effects, which are of increasing concern when it comes to scalable culturing of adhesive cells for regenerative purposes. As a solution to this problem, the employment of synthetic poly(acryl amide) (PAAm)-based hydrogel beads with tissue-matched mechanical properties are proposed as soft matrix for culture modes suitable for tidal bioreactor culture. Herein, technology is described to generate spherical, mm-scaled PAAm hydrogel beads with adjustable, soft elastic properties that are produced by a continuous microfluidic approach. A simple and robust method is demonstrated to functionalize the spheroids with protein ligands, and the suitability of the matrix for cell cultivation is successfully demonstrated with three different cell types (murine mesenchymal stem cells, renal carcinoma cells, and human induced pluripotent stem cells) in model experiments and in a tidal bioreactor system. This versatile approach will pave the way toward novel cell culture systems based on bioreactors that allow scalable, soft carrier-based expansion of cells on matrices with tissue-matched elasticity.