Comparative proteomic analysis of bone marrow mononuclear cells and peripheral blood mononuclear cells for autologous therapeutic implantation in chronic wounds

Abstract Background Chronic wounds represent a complex pathological condition necessitating innovative therapeutic approaches. Cell therapy offers potential for immune modulation and tissue regeneration; however, the therapeutic factors involved in autologous implantations remain insufficiently explored. This study aimed to investigate the molecular properties of mononuclear cells (MNC) from bone marrow (BM) or peripheral blood (PB) sources for autologous cell implantations in patients with chronic wounds. Materials and methods In this single‐centre cohort study, whole‐cell protein lysates from BM‐MNC and PB‐MNC were collected from eight patients with chronic wounds prior to autologous cell implantation and analysed using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Protein abundance was compared between cell sources, including the PB‐MNC control. For protein identification, the peptide identification data were compared with the UniProt Homo sapiens database. Chronic wound outcomes were observed within 6 months. Results Five of the eight patients achieved over 50% wound healing within 6 months. BM‐MNC samples showed protein concentrations of 1.797–2.170 mg/mL, while PB‐MNC samples ranged from 2.363 to 2.939 mg/mL. Principal component (PC) analysis showed clear separation between BM‐MNC and PB‐MNC along PC 1 (27.4% of variance), with 16 proteins significantly differentially expressed between the two sources ( q < 0.05). Compared with control MNC, 25 proteins differed in BM‐MNC and 90 in PB‐MNC, with Annexin and Gelsolin as the only significantly altered proteins in each comparison, respectively. PB‐MNC showed upregulation of proteins linked to immune activation, cytoskeletal remodelling, and coagulation, whereas BM‐MNC retained a more quiescent, niche‐resident protein signature. Conclusions BM‐MNC and PB‐MNC exhibit distinct, source‐specific proteomic signatures. PB‐MNC may represent a less invasive alternative to BM‐MNC for chronic wound cell therapy, though molecular differences and their potential clinical implications warrant confirmation in larger cohorts. Pre‐implantation protein profiling may help distinguish responders from non‐responders and warrants further investigation as a potential precision‐medicine approach to autologous cell therapy.