title: Selected renal cells modulate disease progression in rodent models of chronic kidney disease via NF-κB and TGF-β1 pathways.
abstract: OBJECTIVE
  Identification of mechanistic pathways for selected renal cell (SRC) therapeutic bioactivity in rodent models of chronic kidney disease.
  
  
  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.
  
  
  CONCLUSIONS
  We identify a paracrine mechanism for SRC immunomodulatory and trophic cues on host renal tissues, catalyzing long-term functional benefits in vivo.
authors.affiliation: Regenerative Medicine, United Therapeutics, 55 TW Alexander Drive, Research Triangle Park, NC 27709, USA.|Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Bruce
authors.affiliation: Regenerative Medicine, United Therapeutics, 55 TW Alexander Drive, Research Triangle Park, NC 27709, USA.|Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Ilagan
authors.affiliation: Regenerative Medicine, United Therapeutics, 55 TW Alexander Drive, Research Triangle Park, NC 27709, USA.|Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.
authors.forename: Kelly I
authors.initials: KI
authors.lastname: Guthrie
authors.affiliation: Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.|Infinium Pathology Consultants LLC, 1805 Wild Fern Dr., Oak Ridge, NC 27310, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Rivera
authors.affiliation: Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.|Gene Therapy Center, Vector Core, University of North Carolina at Chapel Hill, NC 27617, USA.
authors.forename: Sumana
authors.initials: S
authors.lastname: Choudhury
authors.affiliation: Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.|Wake Forest Institute for Regenerative Medicine, Medical Centre Boulevard, Winston-Salem, NC 27157, USA.
authors.forename: Namrata
authors.initials: N
authors.lastname: Sangha
authors.affiliation: Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.|RegenMedTX LLC, 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Spencer
authors.affiliation: Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.|RegenMedTX LLC, 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Bertram
authors.affiliation: Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.|RegenMedTX LLC, 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Jain
authors.affiliation: Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.|Burroughs Wellcome Fund, 21 TW Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Kelley
authors.affiliation: Tengion, Inc., 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.|RegenMedTX LLC, 3929 Westpoint Blvd, Ste G, Winston-Salem, NC 27103, USA.
authors.forename: Joydeep
authors.initials: J
authors.lastname: Basu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D055647:Rats, Transgenic; D011924:Rats, Zucker; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1
keywords: NF-κB; PAI-1; cell therapy; chronic kidney disease; fibrosis; inflammation; mechanism of action; miRNA; paracrine; regeneration; selected renal cell; stem cell; tissue engineering; vesicle