title: Circulating progenitor and angiogenic cell frequencies are abnormally static over pregnancy in women with preconception diabetes: A pilot study.
abstract: Type 1 and 2 diabetes decrease the frequencies and functional capacities of circulating angiogenic cells (CAC). Diabetes also elevates gestational complications. These observations may be interrelated. We undertook pilot studies to address the hypothesis that preconception diabetes deviates known gestational increases in CACs. Cross-sectional study of type 1 diabetic, type 2 diabetic and normoglycemic pregnant women was conducted at 1st, 2nd, and 3rd trimester and compared to a 6mo postpartum surrogate baseline. Circulating progenitor cells (CPC; CD34+CD45dimSSlow) and CACs (CD34+CD45dimSSlow expressing CD133 without or with KDR) were quantified by flow cytometry and by colony assay (CFU-Hill). In pregnant normoglycemic women, CD34+CD45dimSSlow cell frequency was greater in 1st and 3rd trimester than postpartum but frequency of these cells was static over type 1 or 2 diabetic pregnancies. Type 1 and type 2 diabetic women showed CACs variance versus normal controls. Type 1 diabetic women had more total CD34+KDR+ CACs in 1st trimester and a higher ratio of CD133+KDR+ to total CD133+ cells in 1st and 2nd trimesters than control women, demonstrating an unbalance in CD133+KDR+ CACs. Type 2 diabetic women had more CD133+KDR+ CACs in 1st trimester and fewer CD133+KDR- CACs at mid-late pregnancy than normal pregnant women. Thus, pregnancy stage-specific physiological fluctuation in CPCs (CD34+) and CACs (CD133+KDR+ and CD133+KDR-) did not occur in type 1 and type 2 diabetic women. Early outgrowth colonies were stable across normal and diabetic pregnancies. Therefore, preconception diabetes blocks the normal dynamic pattern of CAC frequencies across gestation but does not alter colony growth. The differences between diabetic and typical women were seen at specific gestational stages that may be critical for initiation of the uterine vascular pathologies characterizing diabetic gestations.
authors.affiliation: Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada.
authors.forename: Patricia D A
authors.identifier: http://orcid.org/0000-0002-6456-2470
authors.initials: PD
authors.lastname: Lima
authors.affiliation: Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada.
authors.forename: Aysha
authors.initials: A
authors.lastname: Tayab
authors.affiliation: Department of Obstetrics and Gynecology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Malia S Q
authors.initials: MS
authors.lastname: Murphy
authors.affiliation: Department of Obstetrics and Gynecology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Pudwell
authors.affiliation: Department of Obstetrics and Gynecology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Graeme N
authors.initials: GN
authors.lastname: Smith
authors.affiliation: Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada.
authors.forename: B Anne
authors.initials: BA
authors.lastname: Croy
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D010865:Pilot Projects; D049590:Postpartum Period; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D018952:Antigens, CD34; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D017493:Leukocyte Common Antigens