title: Functional evaluation of primary renal cell/biomaterial neo-kidney augment prototypes for renal tissue engineering.
abstract: Development of a tissue-engineered neo-kidney augment (NKA) requires evaluation of defined, therapeutically relevant cell and cell/biomaterial composites (NKA constructs) for regenerative potential in mammalian kidney. Previous work identified primary renal cell populations that extended  survival and improved renal function in a rodent model of chronic kidney disease (CKD). This study extends that work toward the goal of developing NKA by (i) screening in vivo inflammatory and fibrotic responses to acellular biomaterials delivered to healthy rodent renal parenchyma, (ii) evaluating  the functionality of renal cell/biomaterial combinations in vitro, (iii) generating NKA constructs by combining therapeutically relevant cell populations with biocompatible biomaterial, and (iv) evaluating in vivo neokidney tissue development in response to NKA constructs delivered to healthy  rodent renal parenchyma. Gelatin and hyaluronic acid (HA)-based hydrogels elicited the least inflammatory and fibrotic responses in renal parenchyma relative to polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) beads or particles and were associated with neovascularization  and cellular infiltration by 4 weeks postimplantation. Renal cell populations seeded onto gelatin or HA-based hydrogels were viable and maintained a tubular epithelial functional phenotype during an in vitro maturation of 3 days as measured by transcriptomic, proteomic, secretomic, and confocal  immunofluorescence assays. In vivo delivery of cell-seeded NKA constructs (bioactive renal cells + gelatin hydrogels) to healthy rodent renal parenchyma elicited neokidney tissue formation at 1 week postimplantation. To investigate a potential mechanism by which NKA constructs could impact  a disease state, the effect of conditioned media on TGF-β signaling pathways related to tubulo-interstitial fibrosis associated with CKD progression was evaluated. Conditioned medium was observed to attenuate TGF-β-induced epithelial-mesenchymal transition (EMT) in vitro in  a human proximal tubular cell line (HK2).
authors: Tengion Inc., Winston-Salem, NC 27103, USA. joydeep.basu@tengion.com
authors: Joydeep
authors: J
authors: Basu
authors: Christopher W
authors: CW
authors: Genheimer
authors: Elias A
authors: EA
authors: Rivera
authors: Richard
authors: R
authors: Payne
authors: Kim
authors: K
authors: Mihalko
authors: Kelly
authors: K
authors: Guthrie
authors: Andrew T
authors: AT
authors: Bruce
authors: Neil
authors: N
authors: Robbins
authors: Darell
authors: D
authors: McCoy
authors: Namrata
authors: N
authors: Sangha
authors: Roger
authors: R
authors: Ilagan
authors: Toyin
authors: T
authors: Knight
authors: Thomas
authors: T
authors: Spencer
authors: Belinda J
authors: BJ
authors: Wagner
authors: Manuel J
authors: MJ
authors: Jayo
authors: Deepak
authors: D
authors: Jain
authors: John W
authors: JW
authors: Ludlow
authors: Craig
authors: C
authors: Halberstadt
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005780:Gelatin / Q000737:chemistry; D020869:Gene Expression Profiling; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007668:Kidney / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020543:Proteome / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D020100:Hydrogels; D020543:Proteome; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin