Human adipose-derived mesenchymal stem cells ameliorate Diabetic Kidney Disease by restoring macrophage efferocytosis.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Diabetic Kidney Disease (DKD) is a major complication driven by chronic inflammation and impaired tissue homeostasis. While mesenchymal stem cells (MSCs) show promise, the precise mechanisms by which human adipose-derived MSCs (hASCs) modulate macrophage-mediated resolution of inflammation remain to be fully elucidated. Methods We integrated single-cell RNA sequencing (scRNA-seq) analysis of human DKD kidneys with in vivo evaluations in db/db mice and in vitro co-culture models. We employed transcriptomic and molecular approaches to systematically investigate how hASCs impact macrophage functional states. Results scRNA-seq revealed a significant dysregulation of phagocytosis and efferocytosis pathways in human DKD macrophages. In vivo, hASCs effectively homed to injured kidneys, improved renal filtration, and attenuated pathological injury. Rather than a simple binary pro-inflammation to anti-inflammatory switch, hASC treatment restored a comprehensive efferocytic program involving multiple functional stages: chemotaxis (GPR132), recognition/engulfment (PARP9, ELMO1, RAC1), and lysosomal digestion/exhaution and polarisation (LAMP1, LIPA, PPAR-γ, ABCA1). This multi-targeted enhancement was accompanied contributed to the efficient clearance of apoptotic cells, reduced renal oxidative stress, and the mitigation of chronic inflammation. Conclusions Our study systematical

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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