title: Adoptive transfer of syngeneic bone marrow-derived cells in mice with obesity-induced diabetes: selenoorganic antioxidant ebselen restores stem cell competence.
abstract: There are conflicting data regarding the effects of transplantation of bone marrow-derived cells (BMDCs) on the severity of diabetes. We therefore inquired whether the competence of BMDCs is preserved on adoptive transfer into diabetic (db/db) mice and how the adoptive transfer of BMDCs affects vascular and metabolic abnormalities in these mice. Recipient db/db mice received infusions of BMDCs prepared from either db/db or non-diabetic heterozygout mice (db/m) mice and effects on endothelium-dependent relaxation, insulin sensitivity, and renal function were evaluated. Recipients of BMDCs from db/m, but not db/db donors showed better glucose control, exhibited striking improvement in endothelium-dependent relaxation in response to acetylcholine, and had partially restored renal function. Improved glucose control was due to enhanced insulin sensitivity, most likely secondary to improved vascular function. Enhanced apoptosis of endothelial progenitor cells under oxidative stress, as well as decreased endothelial progenitor cell numbers were responsible for the apparent functional incompetence of BMDCs from db/db donors. Treatment of db/db mice with Ebselen restored the resistance of both BMDCs and endothelial progenitor cells to oxidative stress, improved acetylcholine-induced vasorelaxation, and reduced proteinuria in db/db recipients of BMDC transplantation. In conclusion, infusion of BMDCs obtained from db/m donors to db/db recipient mice benefited macrovascular function, insulin sensitivity, and nephropathy. BMDCs obtained from db/db mice were functionally incompetent secondary to the increased proportion of apoptotic cells on oxidative stress challenge; their competence was restored by Ebselen therapy.
authors.affiliation: Department of Medicine, New York Medical College, Valhalla, New York, USA. Jun-Chen@nymc.edu
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Houwei
authors.initials: H
authors.lastname: Li
authors.forename: Francesco
authors.initials: F
authors.lastname: Addabbo
authors.forename: Fung
authors.initials: F
authors.lastname: Zhang
authors.forename: Edward
authors.initials: E
authors.lastname: Pelger
authors.forename: Daniel
authors.initials: D
authors.lastname: Patschan
authors.forename: Hyeong-Cheon
authors.initials: HC
authors.lastname: Park
authors.forename: Mei-Chuan
authors.initials: MC
authors.lastname: Kuo
authors.forename: Jei
authors.initials: J
authors.lastname: Ni
authors.forename: Glenda
authors.initials: G
authors.lastname: Gobe
authors.forename: Praveen N
authors.initials: PN
authors.lastname: Chander
authors.forename: Alberto
authors.initials: A
authors.lastname: Nasjletti
authors.forename: Michael S
authors.initials: MS
authors.lastname: Goligorsky
mesh_terms: D019264:Adoptive Transfer; D000682:Amyloid / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000601:surgery*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005934:Glucagon / Q000097:blood; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D058228:Islet Amyloid Polypeptide; D054833:Isoindoles; D051379:Mice; D008817:Mice, Mutant Strains; D009765:Obesity / Q000150:complications; D016566:Organoselenium Compounds / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D014185:Transplantation, Isogeneic; D014664:Vasodilation / Q000502:physiology
chemical_list: D000682:Amyloid; D000975:Antioxidants; D001393:Azoles; D016207:Cytokines; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D005934:Glucagon