Roberta Cappellari1, Marianna D'Anna1, Angelo Avogaro1, Gian Paolo Fadini2. 1. Department of Medicine, University of Padova, 35128 Padova, Italy; Venetian Institute of Molecular Medicine, 35128 Padova, Italy. 2. Department of Medicine, University of Padova, 35128 Padova, Italy; Venetian Institute of Molecular Medicine, 35128 Padova, Italy. Electronic address: gianpaolo.fadini@unipd.it.
Abstract
BACKGROUND AND AIMS: Diabetes damages the endothelium and reduces the availability of bone marrow (BM)-derived endothelial progenitor cells (EPCs). The mobilization of hematopoietic stem cells (HSCs) and EPCs in response to G-CSF is impaired by diabetes, owing to CXCL12 dysregulation. We have previously shown that the CXCR4/CXCL12 disruptor plerixafor rescues HSC and EPC mobilization in diabetes. We herein explored the effects of plerixafor on HSCs, EPCs, and circulating endothelial cells (CECs) in patients with and without diabetes. METHODS: We re-analysed data gathered in the NCT02056210 trial, wherein patients with (n = 10) and without diabetes (n = 10) received plerixafor to test stem/progenitor cell mobilization. We applied a novel and very specific polychromatic flow cytometry (PFC) approach to identify and quantify HSCs, EPCs, and CECs. RESULTS: We found that 7-AAD(-)Syto16(+)CD34(+)CD45(dim) HSC levels determined by PFC strongly correlated to the traditional enumeration of CD34(+) cells, whereas 7-AAD(-)Syto16(+)CD34(+)CD45(neg)KDR(+) EPCs were unrelated to the traditional enumeration of CD34(+)KDR(+) cells. Using PFC, we confirmed that plerixafor induces rapid mobilization of HSCs and EPCs in both groups, with a marginally significant defect in patients with diabetes. Plerixafor reduced live (7-AAD(-)) and dead (7-AAD(+)) Syto16(+)CD34(bright)CD45(neg)CD146(+) CECs more in patients without than in those with diabetes. The EPC/CEC ratio, a measure of the vascular health balance, was increased by plerixafor, but less prominently in patients with that in those without diabetes. CONCLUSIONS: In addition to rescuing defective mobilization associated with diabetes, plerixafor improves the balance between EPCs and CECs, but the latter effect is blunted in patients with diabetes.
BACKGROUND AND AIMS: Diabetes damages the endothelium and reduces the availability of bone marrow (BM)-derived endothelial progenitor cells (EPCs). The mobilization of hematopoietic stem cells (HSCs) and EPCs in response to G-CSF is impaired by diabetes, owing to CXCL12 dysregulation. We have previously shown that the CXCR4/CXCL12 disruptor plerixafor rescues HSC and EPC mobilization in diabetes. We herein explored the effects of plerixafor on HSCs, EPCs, and circulating endothelial cells (CECs) in patients with and without diabetes. METHODS: We re-analysed data gathered in the NCT02056210 trial, wherein patients with (n = 10) and without diabetes (n = 10) received plerixafor to test stem/progenitor cell mobilization. We applied a novel and very specific polychromatic flow cytometry (PFC) approach to identify and quantify HSCs, EPCs, and CECs. RESULTS: We found that 7-AAD(-)Syto16(+)CD34(+)CD45(dim) HSC levels determined by PFC strongly correlated to the traditional enumeration of CD34(+) cells, whereas 7-AAD(-)Syto16(+)CD34(+)CD45(neg)KDR(+) EPCs were unrelated to the traditional enumeration of CD34(+)KDR(+) cells. Using PFC, we confirmed that plerixafor induces rapid mobilization of HSCs and EPCs in both groups, with a marginally significant defect in patients with diabetes. Plerixafor reduced live (7-AAD(-)) and dead (7-AAD(+)) Syto16(+)CD34(bright)CD45(neg)CD146(+) CECs more in patients without than in those with diabetes. The EPC/CEC ratio, a measure of the vascular health balance, was increased by plerixafor, but less prominently in patients with that in those without diabetes. CONCLUSIONS: In addition to rescuing defective mobilization associated with diabetes, plerixafor improves the balance between EPCs and CECs, but the latter effect is blunted in patients with diabetes.
Authors: Susanna S Park; Elad Moisseiev; Gerhard Bauer; Johnathon D Anderson; Maria B Grant; Azhar Zam; Robert J Zawadzki; John S Werner; Jan A Nolta Journal: Prog Retin Eye Res Date: 2016-10-23 Impact factor: 21.198
Authors: Guy S Taylor; Andy Shaw; Kieran Smith; Tess E Capper; Jadine H Scragg; Michael Cronin; Ayat Bashir; Anneliese Flatt; Matthew D Campbell; Emma J Stevenson; James A Shaw; Mark Ross; Daniel J West Journal: Sci Rep Date: 2021-07-15 Impact factor: 4.379