Abstract: SA-PO0128
Metabolic Reprogramming of B Cells Can Be Reshaped by Mesenchymal Stem Cells in Ischemic AKI
Session Information
- AKI: Mechanisms - 3
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Lee, Kyungho, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Jeon, Junseok, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Lee, Jung eun, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Huh, Wooseong, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Jang, Hye Ryoun, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
Background
Lymphocytes are regulated by metabolic programming and play a role in repair after AKI. The mechanism by which mesenchymal stem cell (MSC)-based therapy enhances organ repair remains incompletely understood, as MSCs do not directly replace damaged tissue. Given that B cells contribute to kidney fibrosis and AKI-to-CKD transition, we hypothesized that 1. AKI induces B cell metabolic reprogramming, and 2. MSC therapy in AKI leads to metabolic rewiring of B cells.
Methods
Moderate-to-severe ischemic AKI was induced by ischemia-reperfusion injury surgery in C57B/6 mice. Mice were treated with Wharton’s jelly MSC (WJ-MSC) or vehicle after AKI. Kidneys were collected at multiple time points, and lymphocytes were isolated and studied with a flow cytometry-based immune-metabolic assay.
Results
B cells underwent metabolic reprogramming after AKI. In the early recovery phase, expression of enzymes related to glycolysis (normalized MFI, Sham vs. AKI, GLUT1 0.73±0.11 vs. 0.33±0.09, P=0.016; HKII 0.65±0.13 vs. 0.25±0.05, P=0.006) and mitochondrial oxidative phosphorylation (OXPHOS) (Tomm20 0.60±0.14 vs. 0.25±0.06, P=0.022) was downregulated. In the late recovery phase, B cells demonstrated a metabolic shift characterized by upregulation of fatty acid oxidation (FAO) (CPT1a 0.30±0.10 vs. 0.76±0.06, P=0.001) and mTOR activity (phospho-S6 0.24±0.09 vs 0.62±0.08, P=0.010). WJ-MSC treatment after AKI modulated these metabolic changes. In the early recovery phase, MSC treatment suppressed FAO (Vehicle vs. MSC, CPT1a 0.73±0.08 vs. 0.43±0.11, P=0.046) and OXPHOS machineries (VDAC1 0.65±0.10 vs. 0.30±0.11, P=0.037; Tomm20 0.58±0.12 vs. 0.21±0.06, P=0.044). In the late recovery phase, MSCs downregulated glycolysis (GLUT1 0.59±0.12 vs. 0.30±0.07, P=0.049; HKII 0.59±0.10 vs. 0.41±0.07, P=0.033) while further enhancing mTOR activity (phospho-S6 0.27±0.07 vs. 0.72±0.10, P=0.004). MSC treatment also induced broader lymphocyte changes, increasing the proportion of CD8+ T cells (22±2.4% vs. 30±2.4%, P=0.032) and decreasing CD4+ (69±2.8% vs. 61±1.9%, P=0.032) and NK T cells (1.10±0.11% vs. 0.73±0.05%, P=0.008).
Conclusion
AKI induced metabolic reprogramming of kidney B cells. WJ-MSC treatment reshaped B cell metabolic profile and altered lymphocyte compositions, suggesting a potential mechanism by which MSC therapy promotes kidney repair following AKI.