Abstract: SA-OR117

Diabetic Kidney Disease (DKD) Alters the Transcriptome in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells (MSC)

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Hickson, LaTonya J., Mayo Clinic, Rochester, Minnesota, United States
  • Eirin, Alfonso, Mayo Clinic, Rochester, Minnesota, United States
  • Saad, Ahmed, Mayo Clinic, Rochester, Minnesota, United States
  • Herrmann, Sandra, Mayo Clinic, Rochester, Minnesota, United States
  • Tang, Hui, 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

Cellular therapy applying autologous MSC may be a viable option for the treatment of DKD. However, patient-related factors, including hyperglycemia and uremia, may alter their reparative capacity. To explore the effect of these biological factors on MSC, we characterized the MSC transcriptome and compared to a set of healthy volunteers (HV).

Methods

MSCs were harvested from subcutaneous abdominal adipose tissue of DKD (n=21) and HV (n=8 kidney donors) subjects. Next-generation sequencing (RNA-seq) of MSC (3rd passage) and functional annotation analysis (DAVID 6.8 database) were then performed to identify differentially expressed mRNAs and rank the primary gene ontology categories.

Results

DKD subjects were older, had higher body mass indices, and lower glomerular filtration rates compared to HV (Table). RNA-seq generated reads for 13,182 mRNAs, of which180 were differentially expressed in DKD-MSC vs. HV-MSC (False Discovery Rate <5% and log2 fold change ≥2 or ≤-2) [Figure]. Functional analysis identified extracellular matrix remodeling and inflammation as the most prominent categories (enrichment score >10), followed by genes capable of modulating cellular pathways linked to tissue repair.

Conclusion

DKD and associated comorbidity modulate the expression of genes involved in inflammation, matrix remodeling, and tissue repair in adipose tissue-derived MSC. These alterations may impact the endogenous repair capacity of MSC and may have clinical implications for the capacity of exogenous autologous MSC delivery to repair DKD.

Funding

  • NIDDK Support