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Abstract: TH-PO638

Adipose-Derived Regenerative Cells: Therapeutic Potential

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

  • Lathan, Rashida, University of Glasgow, Glasgow, United Kingdom
  • Ghita, Ryan, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom
  • Mark, Patrick B., University of Glasgow, Glasgow, United Kingdom
  • Clancy, Marc J., NHS Greater Glasgow and Clyde, Glasgow, United Kingdom
  • Touyz, Rhian, Glasgow University, Glasgow, GLASGOW, United Kingdom

Group or Team Name

  • Marc Clancy and Patrick Mark Team
Background

Studies in our hybrid rat model of transplantation/ischemic reperfusion injury (IRI) have demonstrated improvement in kidney function post injection of adipose-derived regenerative cells (ADRCs) into the renal artery. This technique has translational value in human transplant surgery as ADRCs provide a robust supply of cells from accessible tissue, do not require culturing, and can be generated/delivered at point of care during the time of transplant. The mechanism on how these cells establish regenerative conditions during IRI remains elusive.

Methods

Flow cytometric analysis was performed on rat ADRCs extracted from inguinal tissue (n=14). Cells were surveyed for markers that identify viability, immune cells, immune cell subsets, epithelial cells, pericytes, and mesenchymal stem cells. Rat ADRC RNA expression for angiogenic, anti-oxidant, and anti-/inflammatory markers were measured by real-time PCR. Whole body imaging and histology was performed to track DiR labelled ADRCs. Protein isolated from the kidney at 1 hour 24, and 48 hours post injection were surveyed with a proteome profile array and through western blotting.

Results

ADRCs appear to be a pleomorphic cell suspension with multiple potential active subsets including T-cells, macrophages and mesenchymal stem cells. RNA expression from whole rat ADRCs indicate production of growth and repair factors, and notably- angiogenin and matrix metallopeptidase-2; and chemokine, CXCL1. ADRCs accumulate in clustered regions of the corpuscle 1 and 24-hours post injection of ADRCs.
Gene expression studies performed on the kidneys at 1, 24, and 48 hours post injection identified an upregulation of angiogenic factors VEGFa and angiogenin; anti-oxidant HO-1; and inflammatory factors IFN-gamma and IL-6 when compared to sham-injected control. Protein profiling indicated an upregulation of TIMP-1 and of ligands important in leukocyte trafficking.

Conclusion

Data in the context of our model, suggest they serve as a vehicle for discrete administration of angiogenic and anti-oxidant factors. Counterintuitively, data also suggests that concomitant to secreting repair factors, at early timepoints, factors are secreted which attract inflammatory-related immune cells. Collectively, changes in RNA and protein levels of leukocyte trafficking-related factors suggest a major role for leukocytes in early IRI repair.

Funding

  • Government Support - Non-U.S.