title: Adipose-derived stem cells from diabetic mice show impaired vascular stabilization in a murine model of diabetic retinopathy.
abstract: Diabetic retinopathy is characterized by progressive vascular dropout with subsequent vision loss. We have recently shown that an intravitreal injection of adipose-derived stem cells (ASCs) can stabilize the retinal microvasculature, enabling repair and regeneration of damaged capillary beds in vivo. Because an understanding of ASC status from healthy versus diseased donors will be important as autologous cellular therapies are developed for unmet clinical needs, we took advantage of the hyperglycemic Akimba mouse as a preclinical in vivo model of diabetic retinopathy in an effort aimed at evaluating therapeutic efficacy of adipose-derived stem cells (mASCs) derived either from healthy, nondiabetic or from diabetic mice. To these ends, Akimba mice received intravitreal injections of media conditioned by mASCs or mASCs themselves, subsequent to development of substantial retinal capillary dropout. mASCs from healthy mice were more effective than diabetic mASCs in protecting the diabetic retina from further vascular dropout. Engrafted ASCs were found to preferentially associate with the retinal vasculature. Conditioned medium was unable to recapitulate the vasoprotection seen with injected ASCs. In vitro diabetic ASCs showed decreased proliferation and increased apoptosis compared with healthy mASCs. Diabetic ASCs also secreted less vasoprotective factors than healthy mASCs, as determined by high-throughput enzyme-linked immunosorbent assay. Our findings suggest that diabetic ASCs are functionally impaired compared with healthy ASCs and support the utility of an allogeneic injection of ASCs versus autologous or conditioned media approaches in the treatment of diabetic retinopathy.
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Cronk
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: Molly R
authors.initials: MR
authors.lastname: Kelly-Goss
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: H Clifton
authors.initials: HC
authors.lastname: Ray
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mendel
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Hoehn
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Bruce
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: Bijan K
authors.initials: BK
authors.lastname: Dey
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Guendel
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Tavakol
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: Ira M
authors.initials: IM
authors.lastname: Herman
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA shayn@virginia.edu.
authors.forename: Shayn M
authors.initials: SM
authors.lastname: Peirce
authors.affiliation: Departments of Biomedical Engineering, Pathology, Pharmacology, and Ophthalmology, University of Virginia, Charlottesville, Virginia, USA; Department of Developmental, Molecular and Chemical Biology and Center for Innovations in Wound Healing Research, School of Medicine, Tufts University, Boston, Massachusetts, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Yates
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D017077:Culture Media, Conditioned; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000628:therapy*; D003930:Diabetic Retinopathy / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D051379:Mice; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology
chemical_list: D017077:Culture Media, Conditioned
keywords: Adipose-derived stem cells; Diabetes; Diabetic retinopathy; Pericyte; Stem cells