Circulating progenitor and angiogenic cell frequencies are abnormally static over pregnancy in women with preconception diabetes: A pilot study.

Patricia D A Lima,Aysha Tayab,Graeme N Smith,Jessica Pudwell,Malia S Q Murphy,Zhilin Chen,B Anne Croy,Maria Cristina Vinci

doi:10.1371/journal.pone.0172988

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.

Highlights

Various circulating, bone marrow-derived, vasculotrophic cell types support vessel repair and neoangiogenesis [1]
Circulating angiogenic cells (CACs), originally termed circulating endothelial progenitor cells (EPCs), were considered a single lineage that differentiated into mature endothelium
Microalbumin to creatinine ratios (M/C) in diabetic patients were >26.63 ± 17.90 mg/mmol

Summary

Introduction

Bone marrow-derived, vasculotrophic cell types support vessel repair and neoangiogenesis [1]. EPCs were phenotypically defined as Lin-CD34+CD45- or CD45dim and reactive with either CD133 or KDR (Kinase insert Domain Receptor; VEGFR2 or CD309) These populations gave rise to two types of colonies in culture [1,2]. Known as “colony forming units (CFU)-Hill” grew with endothelial cell-like morphology, they are known to include myeloid cells (macrophages and monocytes) and to have frequent T cell contamination. Cells forming these mixed colonies are still thought to promote angiogenesis and vascular repair [3]. We addressed the dual impacts of diabetes and pregnancy on CPCs (CD34 +CD45dimSSlow), CACs (CD34+CD45dimSSlow expressing CD133 and/or KDR) and on early outgrowth colonies

Objectives

Methods

Results

Conclusion