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Abstract: FR-PO383

Effect of Stromal Cell-Derived Factor 1α Bio-Functionalization on Tissue Formation of Vascular In Situ Tissue Engineered Grafts in Rats With CKD

Session Information

Category: Development‚ Stem Cells‚ and Regenerative Medicine

  • 500 Development‚ Stem Cells‚ and Regenerative Medicine

Authors

  • Krebber, Merle M., Universitair Medisch Centrum Utrecht, Utrecht, Utrecht, Netherlands
  • Besseling, Paul J., Universitair Medisch Centrum Utrecht, Utrecht, Utrecht, Netherlands
  • Fledderus, Joost O., Universitair Medisch Centrum Utrecht, Utrecht, Utrecht, Netherlands
  • Dankers, Patricia Y.W., Technische Universiteit Eindhoven, Eindhoven, Noord-Brabant, Netherlands
  • Bouten, Carlijn V.C., Technische Universiteit Eindhoven, Eindhoven, Noord-Brabant, Netherlands
  • Verhaar, Marianne C., Universitair Medisch Centrum Utrecht, Utrecht, Utrecht, Netherlands

Group or Team Name

  • 1Valve, Materials Driven Regeneration
Background

In situ tissue engineering (TE) offers cell-free scaffolds that transform into living grafts. However, the pro-inflammatory chronic kidney disease (CKD) environment might influence neo-tissue formation. Stromal cell-derived factor 1α (SDF-1α) bio-functionalization may attract and guide host cells with anti-inflammatory and neo-tissue-stimulating properties. Therefore, we studied the role of SDF-1α on initial inflammation and remodeling of vascular grafts in CKD and healthy rats.

Methods

CKD was induced in female rats (n=53) by 5/6th nephrectomy. Upon 50 mg/24h proteinuria, CKD or sham-operated rats underwent abdominal aorta-replacement with an electrospun biodegradable supramolecular polyurethane-131-bisurea (PCU-131-BU) graft, bare or SDF-1α bio-functionalized. Explantation was performed at 2 weeks (preliminary: sham + bare n=4, CKD + bare n=4, sham + SDF-1α n=4, CKD + SDF-1α n=7) or during remodeling (12 weeks, preliminary: sham + bare n=2 and Sham + SDF-1α n=6). Explants were checked for inflammation, tissue formation and graft integrity.

Results

At 2 weeks, immunohistochemistry (IHC) on explants showed that CKD decreased anti-inflammatory macrophage (CD163) presence. The combined presence of CKD and SDF-1α determined Elastin, pan-macrophage inflammation (CD68) and smooth muscle cell Calponin. Fibroblast marker Vimentin was similar in all conditions. Due to progressive proteinuria in n=11 animals, no 12 weeks explants were included for CKD. Vascular rupture and sudden death occurred in 4/15 sham from 3 weeks onwards (2 bare and 2 SDF-1α), possibly related to premature graft resorption. With IHC we indeed found PCU-131-BU fibers in 2-but not in 12 weeks explants. In sham at 12 weeks, SDF-1α led to a non-significant increase of Elastin but no other differences. While patent, all n=9 explants at 12 weeks showed severe vascular dilatation.

Conclusion

In situ TE with PCU-131-BU led to a remodeling response, replacing the synthetic material by vascular tissue. Resorption and mechanical stability may dictate outcomes at least in equal amount to disease and bio-functionalization. SDF-1α may mediate inflammation and tissue-formation in CKD at 2 weeks but during later remodeling under healthy conditions, function appears limited.

Funding

  • Government Support – Non-U.S.