Circulating Pro-Vascular Progenitor Cell Depletion During Type 2 Diabetes: Translational Insights Into the Prevention of Ischemic Complications in Diabetes

Daniella C Terenzi; Mohammed Al-Omran; Adrian Quan; Hwee Teoh; Subodh Verma; David A Hess

doi:10.1016/j.jacbts.2018.10.005

Circulating Pro-Vascular Progenitor Cell Depletion During Type 2 Diabetes: Translational Insights Into the Prevention of Ischemic Complications in Diabetes

JACC Basic Transl Sci. 2018 Nov 5;4(1):98-112. doi: 10.1016/j.jacbts.2018.10.005. eCollection 2019 Feb.

Authors

Daniella C Terenzi^{1

2}, Mohammed Al-Omran^{2

3

4

5}, Adrian Quan¹, Hwee Teoh^{1

6}, Subodh Verma^{1

2

4

5}, David A Hess^{3

5

7}

Affiliations

¹ Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
² Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
³ Division of Vascular Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
⁴ Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
⁵ Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
⁶ Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
⁷ Robarts Research Institute, London, Ontario, Canada.

Abstract

Detection of vascular regenerative cell exhaustion is required to combat ischemic complications during type 2 diabetes mellitus (T2D). We used high aldehyde dehydrogenase (ALDH) activity and surface marker co-expression to develop a high-throughput flow cytometry-based assay to quantify circulating proangiogenic and proinflammatory cell content in the peripheral blood of individuals with T2D. Circulating proangiogenic monocytes expressing anti-inflammatory M2 markers were decreased in patients with T2D. Individuals with longer duration of T2D exhibited reduced frequencies of circulating proangiogenic ALDH^hiCD34+ progenitor cells with primitive (CD133) and migratory (CXCR4) phenotypes. This approach consistently detected increased inflammatory cell burden and decreased provascular progenitor content in individuals with T2D.

Keywords: ALDH, aldehyde dehydrogenase; BM, bone marrow; HbA1c, glycosylated hemoglobin; ROS, reactive oxygen species; SSC, side scatter; T2D, type 2 diabetes mellitus; Wnt, wingless related integration site; aldehyde dehydrogenase; angiogenesis; ischemia; progenitor cells; type 2 diabetes.