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次最大运动期间循环祖细胞动员的动力学

Kinetics of circulating progenitor cell mobilization during submaximal exercise.

作者信息

Niemiro Grace M, Parel Justin, Beals Joseph, van Vliet Stephan, Paluska Scott A, Moore Daniel R, Burd Nicholas A, De Lisio Michael

机构信息

Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois.

Department of Family Medicine, University of Illinois at Urbana-Champaign, Champaign, Illinois.

出版信息

J Appl Physiol (1985). 2017 Mar 1;122(3):675-682. doi: 10.1152/japplphysiol.00936.2016. Epub 2017 Jan 12.

DOI:10.1152/japplphysiol.00936.2016
PMID:28082336
Abstract

Circulating progenitor cells (CPCs) are a heterogeneous population of stem/progenitor cells in peripheral blood that includes hematopoietic stem and progenitor cells (HSPCs and HSCs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs) that are involved in tissue repair and adaptation. CPC mobilization during exercise remains uncharacterized in young adults. The purpose of this study was to investigate the kinetics of CPC mobilization during and after submaximal treadmill running and their relationship to mobilization factors. Seven men [age = 25.3 ± 2.4 yr, body mass index = 23.5 ± 1.0 kg/m, peak O uptake (V̇o) = 60.9 ± 2.74 ml·kg·min] ran on a treadmill for 60 min at 70% V̇o Blood sampling occurred before (Pre), during [20 min (20e), 40 min (40e), 60 min (60e)], and after exercise [15 min (15p), 60 min (60p), 120 min (120p)] for quantification of CPCs (CD34), HSPCs (CD34/CD45), HSCs (CD34/CD45/CD38), CD34 MSCs (CD45/CD34/CD31/CD105), CD34 MSCs (CD45/CD34/CD31/CD105), and EPCs (CD45/CD34/CD31) via flow cytometry. CPC concentration increased compared with Pre at 20e and 40e (2.7- and 2.4-fold, respectively, < 0.05). HSPCs and HSCs increased at 20e compared with 60p (2.7- and 2.8-fold, respectively, < 0.05), whereas EPCs and both MSC populations did not change. CXC chemokine ligand (CXCL) 12 (1.5-fold; < 0.05) and stem cell factor (1.3-fold; < 0.05) were increased at 40e and remained elevated postexercise. The peak increase in CPCs was positively correlated to concentration of endothelial cells during exercise with no relationship to CXCL12 and SCF. Our data show the kinetics of progenitor cell mobilization during exercise that could provide insight into cellular mediators of exercise-induced adaptations, and have implication for the use of exercise as an adjuvant therapy for CPC collection in hematopoietic stem cell transplant. Using a comprehensive evaluation of circulating progenitor cells (CPCs), we show that CPC mobilization during exercise is related to tissue damage, and not plasma concentrations of CXC chemokine ligand 12 and stem cell factor. These data have implications for the use of exercise interventions as adjuvant therapy for CPC mobilization in the context of hematopoietic stem cell transplant and also support the role of mobilized progenitor cells as cellular mediators of systemic adaptations to exercise.

摘要

循环祖细胞(CPCs)是外周血中一类异质性的干细胞/祖细胞群体,包括参与组织修复和适应过程的造血干细胞和祖细胞(HSPCs和HSCs)、内皮祖细胞(EPCs)以及间充质干细胞(MSCs)。在年轻人中,运动期间CPC的动员情况尚不明确。本研究旨在调查次极量跑步机跑步期间及之后CPC动员的动力学变化及其与动员因子的关系。7名男性[年龄=25.3±2.4岁,体重指数=23.5±1.0kg/m²,峰值摄氧量(V̇O₂)=60.9±2.74ml·kg⁻¹·min⁻¹]在跑步机上以70%V̇O₂的强度跑60分钟。在运动前(Pre)、运动期间[20分钟(20e)、40分钟(40e)、60分钟(60e)]以及运动后[15分钟(15p)、60分钟(60p)、120分钟(120p)]进行血液采样,通过流式细胞术对CPCs(CD34)、HSPCs(CD34/CD45)、HSCs(CD34/CD45/CD38)、CD34⁺MSCs(CD45⁻/CD34⁺/CD31⁻/CD105⁺)、CD34⁻MSCs(CD45⁻/CD34⁻/CD31⁻/CD105⁺)和EPCs(CD45⁻/CD34⁺/CD31⁺)进行定量分析⸱。与Pre相比,CPC浓度在20e和40e时升高(分别为2.7倍和2.4倍,P<0.05)⸱。与60p相比,HSPCs和HSCs在20e时升高(分别为2.7倍和2.8倍,P<0.05),而EPCs以及两种MSCs群体均无变化⸱。CXC趋化因子配体(CXCL)12在40e时升高(1.5倍;P<0.05),并在运动后仍保持升高⸱。干细胞因子在40e时升高(1.3倍;P<0.05),并在运动后仍保持升高⸱。CPCs的峰值升高与运动期间内皮细胞浓度呈正相关,与CXCL12和干细胞因子无关⸱。我们的数据显示了运动期间祖细胞动员的动力学变化,这可能有助于深入了解运动诱导适应的细胞介质,并对将运动用作造血干细胞移植中CPC采集的辅助治疗具有启示意义⸱。通过对循环祖细胞(CPCs)进行全面评估,我们发现运动期间CPC的动员与组织损伤有关,而与CXC趋化因子配体12和干细胞因子的血浆浓度无关⸱。这些数据对于将运动干预用作造血干细胞移植背景下CPC动员的辅助治疗具有启示意义,同时也支持动员的祖细胞作为全身运动适应的细胞介质的作用⸱。

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