Construction, Phenotypic Characterization, and Immunomodulatory Function Study of BMSC-Macrophage Hybrid in vitro

Background Immune-mediated kidney diseases are characterized by the deposition of circulating or in-situ immune complexes as their primary pathological feature. Traditional treatments for these conditions have demonstrated limited efficacy. Macrophages possess phagocytic activity towards immune complexes; however, their phenotypes are susceptible to alterations induced by the inflammatory microenvironment. Conversely, bone marrow mesenchymal stem cells (BMSCs) can exert anti-inflammatory functions through paracrine secretion, although they lack phagocytic properties. The interaction between macrophages and BMSCs can enhance anti-inflammatory, anti-oxidative, and vascular repair mechanisms, albeit limited by the spatial separation between them. Further research is warranted to enhance the synergistic effects of macrophages and BMSCs in the context of immune nephropathy. Methods We investigated a novel approach for fusing macrophages with BMSCs through the transient transfection of the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human angiotensin-converting enzyme 2 (hACE2). Magnetic separation technology was utilized for purification. We assessed the efficiency of the resulting hybrids in immunoglobulin G (IgG) clearance, their infiltration into kidney organoids, and their reparative capabilities in the MPC5 injury model, as well as their immunomodulatory effects on immature dendritic cells (iDCs). Additionally, nanovesicles derived from the hybrids were prepared to evaluate their clearance ability concerning interleukin-6 (IL-6). Furthermore, chloroplasts and carbon dots (C-dots) were incorporated to assess the adaptability of the hybrids in ischemic and hypoxic environments. Results The hybrids effectively cleared IgG while preserving their anti-inflammatory and antioxidant properties. They promoted recovery from podocyte injury and inhibited iDCs. Hybrid-derived nanovesicles exhibited the capability to target IgG-enriched regions and adsorb IL-6. Furthermore, chloroplast transplantation improved light energy utilization, thereby enhancing antioxidant capacity and promoting wound repair, while C-dots increased resistance to oxidative damage. Conclusions Our findings suggest that hybrid-mediated therapy represents an innovative and effective strategy for managing immunological renal injury diseases.