title: Diabetes irreversibly depletes bone marrow-derived mesenchymal progenitor cell subpopulations.
abstract: Diabetic vascular pathology is largely attributable to impairments in tissue recovery from hypoxia. Circulating progenitor cells have been postulated to play a role in ischemic recovery, and deficiencies in these cells have been well described in diabetic patients. Here, we examine bone marrow-derived mesenchymal progenitor cells (BM-MPCs) that have previously been shown to be important for new blood vessel formation and demonstrate significant deficits in the context of diabetes. Further, we determine that this dysfunction is attributable to intrinsic defects in diabetic BM-MPCs that are not correctable by restoring glucose homeostasis. We identify two transcriptionally distinct subpopulations that are selectively depleted by both type 1 and type 2 diabetes, and these subpopulations have provasculogenic expression profiles, suggesting that they are vascular progenitor cells. These results suggest that the clinically observed deficits in progenitor cells may be attributable to selective and irreversible depletion of progenitor cell subsets in patients with diabetes.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA Program in Biomedical Informatics, Stanford University School of Medicine, Stanford, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Januszyk
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Sorkin
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Glotzbach
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Ivan N
authors.initials: IN
authors.lastname: Vial
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Zeshaan N
authors.initials: ZN
authors.lastname: Maan
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rennert
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Dominik
authors.initials: D
authors.lastname: Duscher
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Hariharan
authors.initials: H
authors.lastname: Thangarajah
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.affiliation: Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA ggurtner@stanford.edu.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000473:pathology; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D010227:Parabiosis; D013234:Stem Cells / Q000502:physiology*; D013524:Surgical Flaps / Q000098:blood supply
chemical_list: D001786:Blood Glucose
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