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Abstract: TH-PO652

Autologous Mesenchymal Stromal Cell Paracrine Function in Diabetics with and Without Kidney Disease

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 502 Development, Stem Cells, and Regenerative Medicine: Clinical

Authors

  • Hickson, LaTonya J., Mayo Clinic, Rochester, Minnesota, United States
  • Eirin, Alfonso, Mayo Clinic, Rochester, Minnesota, United States
  • Conley, Sabena, Mayo Clinic, Rochester, Minnesota, United States
  • Saad, Ahmed, Mayo Clinic/ Loyola University Medical Center, Naperville, Illinois, United States
  • Mehta, Ramila A., Mayo Clinic, Rochester, Minnesota, United States
  • Tang, Hui, Mayo Clinic, Rochester, Minnesota, United States
  • Saadiq, Ishran M., Mayo Clinic, Rochester, Minnesota, United States
  • Woollard, John R., Mayo Clinic, Rochester, Minnesota, United States
  • Herrmann, Sandra, Mayo Clinic, Rochester, Minnesota, United States
  • Textor, Stephen C., Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic, Rochester, Minnesota, United States
Background

Cell-based therapy applying autologous mesenchymal stromal cells (MSCs) is a promising treatment option for diabetic kidney disease (DKD). MSC provide immunomodulatory, antioxidant, anti-fibrotic, and pro-angiogenic effects in the diseased kidney, but the diabetic and/or uremic milieu may diminish their regenerative capacity in humans. To test the relative contributions of these milieus, we studied MSC paracrine function in patients with diabetes with and without reduced kidney function.

Methods

MSCs were harvested from subcutaneous abdominal fat tissue of DKD subjects (n=44) and Controls (n=6 kidney donors). Levels of secreted cytokines [VEGF, hepatocyte growth factor (HGF; angiogenesis), indoleamine 2,3-dioxygenase (IDO; immunomodulation)] were measured in conditioned media from 3rd passage MSC. MSC functional capacity was measured by migration and proliferation assays.

Results

DKD subjects were older (67±7 vs 47±22 years), had higher BMI (35±6 vs 30±4 kg/m2), and lower eGFR (46±20 vs 92±24 mL/min/1.73m2; all p<0.05), while sex (females 41% vs 67%) and race (whites 84% vs 100%; all p>0.2) were similar to controls. eGFR was <60 in 36 (82%) DKD subjects. DKD-MSC migration and proliferation were reduced compared to Control-MSC (Figure) and their IDO secretion was lower. Yet, VEGF secretion was similar and HGF was increased in DKD-MSC. Most study differences between DKD-MSC and Control-MSC were independent of kidney function.

Conclusion

Diabetes blunts the migration and proliferation capacity of human MSC in vitro, with little further contribution by a fall in kidney function. Nonetheless, angiogenic cytokines important for kidney regeneration are relatively intact, supporting MSC suitability for autologous cell-based therapy in DKD patients.

MSC Function and Paracrine Activity in Diabetes Subjects (eGFR≥60; eGFR<60 mL/min/1.73m2) and Controls

Funding

  • NIDDK Support