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Kidney Week

Abstract: FR-PO1114

Non-Cultured Adipose-Derived Regenerative Cells Limit Early Inflammation and Fibrosis in Renal Ischemia-Reperfusion Injury

Session Information

  • Transplantation: Basic
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 1901 Transplantation: Basic

Authors

  • Lathan, Rashida, University of Glasgow, Glasgow, United Kingdom
  • Mark, Patrick B., University of Glasgow, Glasgow, United Kingdom
Background

Studies in our rat model of ischemic reperfusion injury (IRI) demonstrate improved kidney function post injection of adipose-derived regenerative cells (ADRC). The mechanism on how these cells induce reparative effects during IRI remains elusive. We investigated ADRC-derived effects within the injured kidney at early timepoints.

Methods

Inguinal rat ADRC or vehicle control were injected via the renal artery of the IRI rat model. At 48 hours and 1-week post-ischemia injury, kidney was evaluated for fibrotic and inflammatory markers through qPCR and western blotting of (n=6-8). Leukocyte quantity was assessed by flow cytometry (n=4-5). Histology was used to measure infiltrative lesions and Masson Trichrome stained collagen accumulation (n=8-20).

Results

ADRC-treated kidneys expressed lower levels of inflammatory gene CXCL12 and significantly lower protein levels of granulocyte macrophage colony-stimulating factor (both p<0.05). In addition, a consistent increase in cytotoxic T-lymphocyte-associated protein 4 transcript was characteristic of ADRC treated kidneys. At 48 hours post-IRI, half of vehicle controls contained higher levels of CD45+ leukocytes. Assessment of leukocyte infiltrate indicated a trend of higher infiltrate in vehicle control kidneys compared to ADRC kidneys at 48 hours with significant apparent differences by 1-week post IRI (p<0.05).
Early accumulation of interstitial factors: tissue inhibitor of metalloproteinase-1 (p<0.05) and collagen type 1, alpha 2 (p<0.001) in vehicle control kidneys indicated early fibrotic development. This was mirrored by significantly high levels of collagen staining in control compared to ADRC treated kidneys at 1-week post IRI (p<0.001).

Conclusion

Collectively, gene, protein expression and histological evidence suggest that ADRC treated IRI kidneys experience early anti-inflammatory changes conducive to the inhibition of fibrogenesis.

Funding

  • Private Foundation Support