Abstract: TH-PO735

Altered Functional Characteristics of Adipose-Derived Mesenchymal Stem/Stromal Cells (MSC) in Diabetic Kidney Disease (DKD)

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Hickson, LaTonya J., Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic, Rochester, Minnesota, United States
  • Saad, Ahmed, Mayo Clinic, Rochester, Minnesota, United States
  • Eirin, Alfonso, Mayo Clinic, Rochester, Minnesota, United States
  • Kirkland, James L., Mayo Clinic, Rochester, Minnesota, United States
  • Tchkonia, Tamara, Mayo Clinic, Rochester, Minnesota, United States
  • Mckenzie, Travis, Mayo Clinic, Rochester, Minnesota, United States
  • Rule, Andrew D., Mayo Clinic, Rochester, Minnesota, United States
  • Palmer, Allyson, Mayo Clinic, Rochester, Minnesota, United States
  • Textor, Stephen C., Mayo Clinic, Rochester, Minnesota, United States
Background

Novel interventions such as MSC to delay the progression of DKD are needed. However, the origin of MSC may affect the regenerative capacity of autologous cell-based therapy. We hypothesized that functional capacity and senescent cell burden of MSC from DKD subjects would be impaired compared to healthy volunteers (HV).

Methods

MSC were cultured from subcutaneous abdominal adipose tissue from 21 subjects with DKD and 5 HV (kidney donors). MSC proliferation, migration, senescence-associated β-galactosidase activity, Activin A, and Annexin V (apoptosis marker) were studied.

Results

DKD subjects were older (65±8 vs 35±16 years; p<0.001), with higher body mass index (37±5 vs 31±4 kg/m2; p=0.03) and lower eGFR [median 40 (IQR: 31, 54) vs 87 (IQR: 76, 114); p<0.001] compared to HV. Race (76% vs 100% white) and sex (43% vs 60% female) were not different. MSC migration and proliferation were decreased in DKD-MSC compared to HV-MSC. Senescence was increased in DKD-MSC, but apoptosis was similar between groups. Similarly, markers of senescence (Activin A) measured in the MSC-cultured media were higher in DKD. [Figure]

Conclusion

DKD-MSC exhibit altered functional characteristics and increased senescence, possibly due to aging and diabetic microenvironments. Diabetes and uremia may alter the function of MSC, potentially limiting the effectiveness of autologous-based therapy.

MSC Function and Senescence Studies - DKD and HV Subjects

Funding

  • NIDDK Support