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Abstract: PO0662

Transcriptomic Alterations of Angiogenesis Activity in Human Mesenchymal Stromal/Stem Cells in Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Conley, Sabena, Mayo Clinic's Campus in Florida, Jacksonville, Florida, United States
  • Bian, Xiaohui, Mayo Clinic's Campus in Florida, Jacksonville, Florida, United States
  • Eirin, Alfonso, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Zimmerman Zuckerman, Eric A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Dehankar, Mrunal K., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Smith, Anastasia L., Mayo Clinic's Campus in Florida, Jacksonville, Florida, United States
  • Gowan, Cody, Mayo Clinic's Campus in Florida, Jacksonville, Florida, United States
  • Snow, Zachary Kayne, Mayo Clinic's Campus in Florida, Jacksonville, Florida, United States
  • Herrmann, Sandra, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Jarmi, Tambi, Mayo Clinic's Campus in Florida, Jacksonville, Florida, United States
  • Lerman, Lilach O., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Hickson, LaTonya J., Mayo Clinic's Campus in Florida, Jacksonville, Florida, United States
Background

Therapeutic interventions that optimize angiogenic activities may reduce rates of end-stage kidney failure and extremity amputations in individuals with diabetic kidney disease (DKD). Autologous mesenchymal stromal cells (MSCs) infusion is a promising novel treatment, but DKD-related factors, including hyperglycemia and uremia, might alter MSC angiogenic repair capacity.

Methods

To explore MSC angiogenic dysregulation in DKD, we characterized the transcriptome of adipose tissue-derived MSC obtained from DKD subjects (DKD-MSC) compared to age-matched controls without diabetes or kidney impairment. Next-generation RNA sequencing (RNA-seq) was performed to identify in MSCs differentially expressed (DE; adjusted p<0.05, |log2fold change| >1) mRNA and miRNA involved in angiogenesis (GeneCards). DE miRNAs were further inspected to identify targets involving interactions with angiogenesis genes (miRWalk and Ingenuity pathway analysis).

Results

Mean age in DKD subjects was 65±8 years, 31% were females, and mean eGFR was 38.9±15.4 mL/min/1.73m2 (n=29), while control subjects (n=9) had higher eGFR (80.5±13.3 mL/min/1.73m2; p<0.0001). RNA-seq analyses revealed 133 DE mRNAs (77 up- and 56 down-regulated) in DKD-MSC compared to Control-MSC. Figure 1A shows the top 30 DE mRNAs. Of 208 DE miRNAs, 14 (Figure 1B) regulated 18 unique DE mRNA targets associated with angiogenesis. Among these miRNAs resulted in pro- and anti-angiogenic regulators including miR-17-5p, let-7d-5p, miR-125a-5p and miR-30c-5p.

Conclusion

MSC from individuals with DKD may have limited angiogenic potential and reparative capacity, warranting caution in autologous MSC transplantation in DKD.

Funding

  • NIDDK Support