Transplantation最新文献

Innovation is a hallmark of organ, tissue, and cell transplantation. The development of new treatments derived from these substances of human origin (SoHO) has rapidly evolved in recent years. Despite the great benefits that these innovative therapies could bring to patients, significant difficulties have arisen in making them equitably and widely accessible. Herein, we identify and address 4 challenges to promote innovation in this field in a collaborative, sustainable, and transparent manner and propose some concrete solutions applicable to SoHO-derived treatments, ranging from cell therapies to solid organ transplantation. Regulators, health policymakers, and government officials are recommended to incorporate specific elements into the regulatory frameworks of their respective jurisdictions, although regulatory convergence and equivalent quality and safety standards applicable to SoHO at a global level would be needed. An innovation-driven regulatory environment, respectful with the human origin and in accordance with the altruistic donation of SoHO, should be encouraged to improve the safety, effectiveness, accessibility, and affordability of SoHO and to promote collaboration between countries and between public and private sectors. This overview is the outcome of a working group focused on "Innovation in the donation and clinical application of SoHO" as part of the international Summit "Towards Global Convergence in Transplantation: Sufficiency, Transparency and Oversight" convened by the Organización Nacional de Trasplantes under the Spanish Presidency of the Council of the European Union in November 2023 and cosponsored by the Council of Europe, the World Health Organization, the Transplantation Society, and the European Society for Organ Transplantation.

Background: Liver transplantation stands as the primary treatment for end-stage liver disease, with demand surging in recent decades because of expanded indications. However, hepatic ischemia/reperfusion injury can lead to liver transplant failure in both deceased donor and living donor transplantation. This study explored whether preconditioning donor livers through exercise training (ExT) could mitigate cold ischemic injury posttransplantation.

Methods: Donor C57BL/6 mice underwent ExT via treadmill running or remained sedentary. After 4 wk, the donor liver underwent cold storage and subsequent orthotopic liver transplantation or ex vivo warm reperfusion.

Results: Donor liver from mice subjected to ExT showed significantly decreased hepatic injury on reperfusion. Tissue histology revealed decreased sinusoidal congestion, vacuolization, and hepatocellular necrosis in livers from ExT mice, and immunofluorescence staining further revealed a decreased number of apoptotic cells in ExT grafts. Livers from ExT donors expressed decreased intragraft inflammatory cytokines cascade, decreased neutrophil infiltration and neutrophil extracellular traps, and increased M2 phenotype of recipient macrophages compared with grafts from sedentary mice. After cold storage, liver grafts from ExT donors showed decreased accumulation of reactive oxygen species and decreased levels of cytochrome c and high mobility group box 1 released in the liver effluent. In addition, ExT grafts showed upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and higher levels of mitochondrial content. Similar effects of decreased hepatic injury were observed in wild-type mice when pretreated with a PGC-1α stimulator ZLN005 instead of ExT.

Conclusions: These findings suggest that augmenting hepatocytic mitochondrial content through donor exercise or PGC-1α stimulation may offer therapeutic avenues to mitigate postreperfusion inflammation and improve transplant outcomes.

Background: Although kidney transplantation (KT) has become the standard of care for people living with HIV (PLWH) suffering from renal failure, early experiences revealed unanticipated higher rejection rates than those observed in HIV- recipients. The cause of increased acute rejection (AR) in PLWH was assessed by performing a transcriptomic analysis of biopsy specimens, comparing HIV+ to HIV- recipients.

Methods: An analysis of 68 (34 HIV+, 34 HIV-) formalin-fixed paraffin-embedded (FFPE) renal biopsies matched for degree of inflammation was performed from KT recipients with acute T cell-mediated rejection (aTCMR), borderline for aTCMR (BL), and normal findings. Gene expression was measured using the NanoString platform on a custom gene panel to assess differential gene expression (DE) and pathway analysis (PA).

Results: DE analysis revealed multiple genes with significantly increased expression in the HIV+ cohort in aTCMR and BL relative to the HIV- cohort. PA of these genes showed enrichment of various inflammatory pathways, particularly innate immune pathways associated with Toll-like receptors.

Conclusions: Upregulation of the innate immune pathways in the biopsies of PLWH with aTCMR and BL is suggestive of a unique immune response that may stem from immune dysregulation related to HIV infection. These findings suggest that these unique HIV-driven pathways may in part be contributory to the increased incidence of allograft rejection after renal transplantation in PLWH.

Establishing transparency and oversight of organ transplantation by regulatory agencies is of paramount importance to assure ethical, legal, and clinically robust transplantation practices. Registries reporting activity and outcome data of the donor and recipient, including donor source (living or deceased), must be developed for each transplant and should be a mandatory requirement to achieve accreditation to perform transplant surgeries. Collected data for the living organ donor must include the nationality, the nature of their relationship with the recipient, and the complications encountered by living donors that result in prolonged morbidity or mortality. Long-term patient and graft survival must be reported for the recipient with the underlying reasons for mortality or graft loss. To retain the authorization to perform organ transplantation, a facility must ensure that it reports this required information regarding every organ transplant.

Background: In total pancreatectomy with islet autotransplantation (TPIAT), a greater number of islets transplanted produces more favorable outcomes. We aimed to determine predictors of islet isolation outcomes.

Methods: We investigated factors associated with islet isolation outcomes expressed as islet number (IN), islet equivalents (IEQ; standardized to an islet with 150 μm diameter), IN/kg, or IEQ/kg using data from the multicenter Prospective Observational Study of TPIAT. Single-predictor linear regression was used to estimate the association of individual patient and disease characteristics with islet isolation outcomes, and augmented backward elimination was used to select variables to include in multivariable analyses.

Results: In multivariable analyses, only elevated hemoglobin A1c was associated with worse outcomes for all measures ( P  < 0.001 for all). Total IEQ obtained for transplant was higher for participants with Hispanic ethnicity ( P  = 0.002) or overweight status pre-TPIAT ( P  < 0.001) and lower with non-White race ( P  = 0.03), genetic pancreatitis ( P  = 0.02), history of lateral pancreaticojejunostomy ( P  = 0.03), and presence of atrophy ( P  = 0.006) or ductal changes ( P  = 0.014) on imaging. IEQ/kg was higher in females ( P  = 0.01) and Hispanic participants ( P  = 0.046) and generally lower with older age (nonlinear association, P  < 0.001) and pancreatic atrophy ( P  < 0.001) on imaging. Total IN and IN/kg showed trends similar, but not identical, to IEQ and IEQ/kg, respectively.

Conclusions: Patient demographics and certain pancreatic disease features were associated with outcomes from islet isolation. Hemoglobin A1c before TPIAT was the metabolic testing measure most strongly associated with islet isolation results.

Living kidney donors (LKDs) undertake a complex and multifaceted journey when pursuing donation and have several unmet healthcare needs. A comprehensive understanding of these needs across their entire donation trajectory can help develop a patient-centered care model. We conducted a scoping review to synthesize empirical evidence, published since 2000, on LKDs' experiences with healthcare from when they decided to pursue donation to postdonation care, and what they reported as their care needs. We categorized them according to the 8 Picker principles of patient-centered care. Of the 4514 articles screened, 47 were included. Ample literature highlighted the need for (1) holistic, adaptable, and linguistically appropriate approaches to education and information; (2) systematic, consistent, and proactive coordination and integration of care; and (3) self-management and preparation to optimize perioperative physical comfort. Some literature highlighted the need for (4) better continuity and transition of care postdonation. Two key unmet needs were the lack of (5) a holistic psychosocial evaluation predonation and predischarge to provide emotional support and alleviation of fear and anxiety; and (6) access to specialty and psychosocial services postdonation especially when adverse events occurred. Limited literature explored the principles of (7) respect for patients' values, preferences, and expressed needs; and (8) involvement of family and friends as caregivers. We summarize several unmet healthcare needs of LKDs throughout their donation journey and highlight knowledge gaps. Addressing them can improve their well-being and experiences, and potentially address inequities in living kidney donation and increase living donor kidney transplantation.