Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions.

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (Tregs), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, Tregs, RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery.

A Practical Guide to Implementing Holistic Review during Surgery Resident Selection.

Provider workforce diversity is a key component of improving healthcare quality and addressing healthcare disparities. Furthermore, the traditional approach of "score-centered" application metrics do not consistently correlate with meeting milestones in surgery, nor do they adequately predict a surgical resident's clinical strength and operative abilities. We present here an adaptable process by which surgical residency programs can identify their values and incorporate holistic review into their resident selection process to improve resident selection and physician workforce diversity.

County socioeconomic characteristics and pediatric renal transplantation outcomes.

BACKGROUND: Existing risk adjustment models for solid organ transplantation omit socioeconomic status (SES). With limited data available on transplant candidates' SES, linkage of transplant outcomes data to geographic SES measures has been proposed. We investigate the utility of county SES for understanding differences in pediatric kidney transplantation (KTx) outcomes. METHODS: We identified patients < 18 years of age receiving first-time KTx using United Network for Organ Sharing registry data in two eras: 2006-2010 and 2011-2015, corresponding to periods of county SES data collection. In each era, counties were ranked by 1-year rates of survival with intact graft, and by county SES score. We used Spearman correlation (ρ) to evaluate the association between county rankings on SES and transplant outcomes in each era and consistency between these measures across eras. We also evaluated the utility of county SES for improving prediction of individual KTx outcomes. RESULTS: The analysis included 2972 children and 108 counties. County SES and transplant outcomes were not correlated in either 2006-2010 (ρ = 0.06; p = 0.525) or 2011-2015 (ρ = 0.162, p = 0.093). County SES rankings were strongly correlated between eras (ρ = 0.99, p < 0.001), whereas county rankings of transplant outcomes were not correlated between eras (ρ = 0.16, p = 0.097). Including county SES quintile in individual-level models of transplant outcomes did not improve model predictive utility. CONCLUSIONS: Pediatric kidney transplant outcomes are unstable from period to period at the county level and are not correlated with county-level SES. Appropriate adjustment for SES disparities in transplant outcomes could require further collection of detailed individual SES data.

L1TD1 is a marker for undifferentiated human embryonic stem cells.

BACKGROUND: Human embryonic stem cells (hESC) are stem cells capable of differentiating into cells representative of the three primary embryonic germ layers. There has been considerable interest in understanding the mechanisms regulating stem cell pluripotency, which will ultimately lead to development of more efficient methods to derive and culture hESC. In particular, Oct4, Sox2 and Nanog are transcription factors known to be important in maintenance of hESC. However, many of the downstream targets of these transcription factors are not well characterized. Furthermore, it remains unknown whether additional novel stem cell factors are involved in the establishment and maintenance of the stem cell state. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that a novel gene, L1TD1 (also known as FLJ10884 or ECAT11), is abundantly expressed in undifferentiated hESC. Differentiation of hESC via embryoid body (EB) formation or BMP4 treatment results in the rapid down-regulation of L1TD1 expression. Furthermore, populations of undifferentiated and differentiated hESC were sorted using the stem cell markers SSEA4 and TRA160. Our results show that L1TD1 is enriched in the SSEA4-positive or TRA160-positive population of hESC. Using chromatin immunoprecipitation we found enriched association of Nanog to the predicted promoter region of L1TD1. Furthermore, siRNA-mediated knockdown of Nanog in hESC also resulted in downregulation of L1TD1 expression. Finally, using luciferase reporter assay we demonstrated that Nanog can activate the L1TD1 upstream promoter region. Altogether, these results provide evidence that L1TD1 is a downstream target of Nanog. CONCLUSION/SIGNIFICANCE: Taken together, our results suggest that L1TD1 is a downstream target of Nanog and represents a useful marker for identifying undifferentiated hESC.