Background Thymic-derived regulatory T cells (tTreg) are critical regulators of the immune system. Adoptive tTreg transfer is a curative therapy for murine models of autoimmunity, graft rejection, and graft versus host disease (GVHD). We previously completed a “first-in-human” clinical trial using in vitro expanded umbilical cord blood (UCB) derived tTreg to prevent GVHD in patients undergoing UCB hematopoietic stem cell transplantation (HSCT). tTreg were safe and demonstrated clinical efficacy, but low yield prevented further dose escalation. Methods To optimize yield, we investigated the use of KT64/86 artificial antigen presenting cells (aAPC) to expand tTreg and incorporated a single re-stimulation after day 12 in expansion culture. Results aAPC increased UCB tTreg expansion >8-fold over CD3/28 stimulation. Re-stimulation with aAPC increased UCB tTreg expansion an additional 20–30 fold. Re-stimulated human UCB tTreg ameliorated GVHD disease in a xenogeneic model. Following cGMP validation, a trial was conducted with tTreg. tTreg doses up to >30-fold higher compared to that obtained with anti-CD3/28 mAb coated-bead expansion and Foxp3 expression was stable during in vitro expansion and following transfer to patients. Increased expansion did not result in a senescent phenotype and GVHD was significantly reduced. Discussion Expansion culture with cGMP aAPC and re-stimulation reproducibly generates sufficient numbers of UCB tTreg that exceeds the numbers of T effector cells in an UCB graft. The methodology supports future tTreg banking and is adaptable to tTreg expansion from HSC sources. Furthermore, since HLA matching is not required, allogeneic UCB tTreg may be a useful strategy for prevention of organ rejection and autoimmune disease.
Career shadowing can be a valuable opportunity for individuals to experience the daily activities of a working professional. However, there is no published research regarding the impact of shadowing for individuals hoping to pursue a career as a genetic counselor (GC) (termed 'shadowees'). Additionally, little is known about the impact of shadowing on practicing GCs, nor the value of shadowing in the application and admission process for genetic counseling graduate programs. For this study, three independent surveys were developed and sent to three stakeholder groups: shadowees in the Minnesota Genetic Counseling Experience Program, program directors within the Association of Genetic Counseling Program Directors, and members of the National Society of Genetic Counselors. Quantitative and qualitative analyses were performed on responses. The survey of shadowees (n = 55) found that the majority believed that shadowing had either a 'very' or 'somewhat positive' impact on their decision to become a GC and on their application to a genetic counseling graduate program (81.8% and 91.3%, respectively). Of the participating program director respondents (n = 43), the majority indicated that having shadowing experience was either 'moderately' or 'extremely important' in offering an interview or for acceptance into a graduate program (63% and 56%, respectively). While programs differ in evaluation of shadowing experiences, most program directors indicated that an applicant's ability to speak to their shadowing experience was the most important factor in admissions consideration (71%). Among the GCs surveyed (n = 325), 69.2% have hosted shadowees; of these, 82.7% indicated that hosting a shadowee decreases their efficiency at work. Despite this drawback, the majority of respondents expressed a willingness and motivation to host shadowees to help the shadowee (64.8%) and to promote the genetic counseling profession (32.
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