title: Early-outgrowth bone marrow cells attenuate renal injury and dysfunction via an antioxidant effect in a mouse model of type 2 diabetes.
abstract: Cell therapy has been extensively investigated in heart disease but less so in the kidney. We considered whether cell therapy also might be useful in diabetic kidney disease. Cognizant of the likely need for autologous cell therapy in humans, we sought to assess the efficacy of donor cells derived from both healthy and diabetic animals. Eight-week-old db/db mice were randomized to receive a single intravenous injection of PBS or 0.5 × 10(6) early-outgrowth cells (EOCs) from db/m or db/db mice. Effects were assessed 4 weeks after cell infusion. Untreated db/db mice developed mesangial matrix expansion and tubular epithelial cell apoptosis in association with increased reactive oxygen species (ROS) and overexpression of thioredoxin interacting protein (TxnIP). Without affecting blood glucose or blood pressure, EOCs not only attenuated mesangial and peritubular matrix expansion, as well as tubular apoptosis, but also diminished ROS and TxnIP overexpression in the kidney of db/db mice. EOCs derived from both diabetic db/db and nondiabetic db/m mice were equally effective in ameliorating kidney injury and oxidative stress. The similarly beneficial effects of cells from healthy and diabetic donors highlight the potential of autologous cell therapy in the related clinical setting.
authors.affiliation: Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.forename: Darren A
authors.initials: DA
authors.lastname: Yuen
authors.forename: Andrew
authors.initials: A
authors.lastname: Advani
authors.forename: Kerri
authors.initials: K
authors.lastname: Thai
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Advani
authors.forename: David
authors.initials: D
authors.lastname: Kepecs
authors.forename: M Golam
authors.initials: MG
authors.lastname: Kabir
authors.forename: Kim A
authors.initials: KA
authors.lastname: Connelly
authors.forename: Richard E
authors.initials: RE
authors.lastname: Gilbert
mesh_terms: D000419:Albuminuria / Q000517:prevention & control; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation; D002352:Carrier Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D008297:Male; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D012235:Rhodamines; D013879:Thioredoxins / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C116572:(((4-chloromethyl)benzoyl)amino)-tetramethylrhodamine; D000975:Antioxidants; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D017382:Reactive Oxygen Species; D012235:Rhodamines; C515559:Txn1 protein, mouse; C445672:Txnip protein, mouse; D013879:Thioredoxins