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Abstract: PO0886

Obesity Blunts the Reparative Function of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Ischemic Murine Kidneys

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Klomjit, Nattawat, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States
  • Krier, James, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States
  • Conley, Sabena, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States
  • Zhu, Xiang yang, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States
  • Ferguson, Christopher M., Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States
  • Jordan, Kyra L., Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States
  • Tang, Hui, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Amir, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Lilach O., Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States
Background

Obesity is a health burden that can affect cellular processes. Mesenchymal stromal/stem cells (MSC) ameliorate renal injury in several diseases. Obesity impairs MSC function in vitro, but its effect on in vivo reparative function of human MSC remains unknown.

Methods

MSC were harvested from non-obese (‘lean’) (body mass index [BMI] <30 kg/m2) and obese (BMI≥30) human subjects during kidney donation or bariatric surgery, respectively. To test their function in vivo, MSC (5x105/200 µL) or vehicle were injected into 129S1 mice 2 weeks after renal artery stenosis (RAS) or sham surgery (n=6-8/group). Two weeks later, mice underwent magnetic resonance imaging to assess renal perfusion and oxygenation, and kidneys then harvested.

Results

A similar number of lean and obese human MSC engrafted in stenotic mouse kidneys. Vehicle-treated RAS mice had reduced cortical and medullary perfusion. Lean (but not obese) MSC normalized cortical perfusion (p=0.2 vs sham+vehicle) (Figure A&B), whereas both effectively mitigated renal hypoxia. Serum creatinine and blood pressure were elevated in all RAS mice, and lowered only by lean MSC (p=0.4 vs sham+vehicle). Both alleviated renal fibrosis in RAS, but lean more effectively than obese MSC (p=0.02). Tubular and glomerular injury was improved similarly by both.

Conclusion

Lean MSC are superior to obese MSC in repairing ischemic kidney injury and blood pressure in murine RAS, implying dysfunction of the endogenous MSC repair system in obese patients. This should also be considered during autologous cell-based approaches.

Funding

  • NIDDK Support