Selected renal cells modulate disease progression in rodent models of chronic kidney disease via NF-κB and TGF-β1 pathways. (October 2015)

• Record Type: Journal Article
• Authors: Bruce, Andrew T; Ilagan, Roger M; Guthrie, Kelly I; Rivera, Elias; Choudhury, Sumana; Sangha, Namrata; Spencer, Thomas; Bertram, Timothy A; Jain, Deepak; Kelley, Russell W; Basu, Joydeep
• Is Part Of: Regenerative medicine. Volume 10:Number 7(2015)
• Page Start: 815
• Page End: 839
• Publication Date: 2015-10
• Subjects: cell therapy -- chronic kidney disease -- fibrosis -- inflammation -- mechanism of action -- miRNA -- NF-κB -- PAI-1 -- paracrine -- regeneration -- selected renal cell -- stem cell -- tissue engineering -- vesicle; Cellular therapy -- Periodicals; Stem cells -- Transplantation -- Periodicals; Degeneration (Pathology) -- Treatment -- Periodicals; Regeneration (Biology) -- Periodicals; 611.018
• DOI: 10.2217/rme.15.43
• Languages: English
• ISSNs: 1746-0751

Abstract

Aim: Identification of mechanistic pathways for selected renal cell (SRC) therapeutic bioactivity in rodent models of chronic kidney disease.Materials & methods: In vivo and in vitro functional bioassays applied to investigate regenerative outcomes associated with delivery of SRC to diseased rodent kidney.Results: In vivo, SRC reduces chronic infiltration by monocytes/macrophages. SRC attenuates NF-κB and PAI-1 responses while simultaneously promoting host tubular cell expansion through trophic cues. In vitro, SRC-derived conditioned media attenuates TNF-α-induced NF-κB response, TGF-β-mediated PAI-1 response and increases expression of transcripts associated with cell cycle regulation. Observed bioactive responses were from vesicle and nonvesicle-associated factors, including specific miRNAs.Conclusion: We identify a paracrine mechanism for SRC immunomodulatory and trophic cues on host renal tissues, catalyzing long-term functional benefits in vivo .