Infusion of young donor plasma components in older patients modifies the immune and inflammatory response to surgical tissue injury: a randomized clinical trial

• DOI: 10.1186/s12967-025-06215-w
• Publication Date: 2025-02-14T18:03:57Z
• Authors: Brice Gaudilliere; Lei Xue; Amy S. Tsai; Xiaoxiao Gao; Tiffany N. McAlli...; Martha Tingle; Gladys Porras; Igor Feinstein; Dorien Feyaerts; Franck Verdonk; Maximilian Sabayev; Julien Hedou; Edward A. Ganio; Eloïse Berson; Martin Becker; Camilo Espinosa; Yeasul Kim; Benoit Lehallier; Esther Rawner; Chunmiao Feng; Derek F. Amanatullah; James I. Huddleston; Stuart B. Goodman; Nima Aghaeepour; Martin S. Angst
• Keywords: Inflammation; Aging; Elderly population; Immune cells; R; Medicine; Tissue injury; Inflammaging

Abstract Background Preclinical evidence suggests that young plasma has beneficial effects on multiple organ systems in aged mice. Whether exerts an aging human population remains highly controversial. Despite lacking data, donor infusions have been promoted for age-related conditions. Given the preclinical by attenuating inflammation, this study examined whether administering a protein fraction to elderly would exert anti-inflammatory and immune modulating humans, using surgery as tissue injury model. Methods This double-blind, placebo-controlled enrolled randomized 38 patients undergoing major joint replacement surgery. Patients received four separate of derived from donors, or placebo one day before surgery, after Blood specimens proteomic immunological analyses were collected each infusion. Based high-content assessment circulating proteins with single-cell peripheral cells, signatures cell-type-specific signaling responses separated treatment groups regression models. Results Elastic net models revealed administration significantly altered (AUC = 0.796, p 0.002) cellular response 0.904, < 0.001) surgical trauma resulting pathway- cell type-specific modulation. Affected pathways regulating inflammation included JAK-STAT, NF-kappa B, MAPK ( 0.001). These findings confirmed at level JAK/STAT diminished IkB, negative regulator NFkB, was elevated adaptive cells. Conclusion Reported provide first proof principle humans actively regulates inflammatory population. They solid rationale elucidating active principles may be therapeutic benefits range pathologies. Trial registration ClinicalTrials.gov, NCT 03981419.