Sustained adenosine release:Revealing its impact on osteogenic signalling pathways of human mesenchymal stromal cells  

作　　者：Hadi Hajiali Jane McLaren Cristina Gonzalez-García Salah Abdelrazig Dong-Hyun Kim Matthew J.Dalby Manuel Salmerón-Sánchez Felicity R.A.J.Rose 

机构地区：[1]School of Pharmacy,Nottingham Biodiscovery Institute,University of Nottingham,Nottingham,UK [2]Healthcare Technologies Institute,School of Chemical Engineering,University of Birmingham,Birmingham,UK [3]Centre for the Cellular Microenvironment,University of Glasgow,Glasgow,UK [4]Centre for Analytical Bioscience,Advanced Materials&Healthcare Technologies Division,School of Pharmacy,University of Nottingham,Nottingham,UK [5]Marine Microbiomics,Program in Biology,Division of Science and Mathematics,New York University Abu Dhabi(NYUAD),P.O.Box 129188,Abu Dhabi,United Arab Emirates

出　　处：《Engineered Regeneration》2024年第2期255-268,共14页再生工程（英文）

基　　金：Financial support was received from Engineering and Physical Sci-ences Research Council(EPSRC);Reference:EP/P001114/;Engineering growth factor microenvironments-a new therapeutic paradigm for re-generative medicine.

摘　　要：Non-healing fractures,a global health concern arising from trauma,osteoporosis,and tumours,can lead to severe disabilities.Adenosine,integral to cellular energy metabolism,gains prominence in bone regeneration via adeno-sine A2 B receptor activation.This study introduces a controlled-release system for localized adenosine delivery,fostering human mesenchymal stromal cell(hMSC)differentiation into functional bone cells.The study investi-gates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive media.Insights into adenosine-modulated signalling pathways during MSC differenti-ation,with osteogenic factors,provide a comprehensive understanding of the pathways involved.Analysing gene expression and metabolic profiles unravels adenosine’s regulatory mechanisms in MSC differentiation.Sustained adenosine release from microparticles induces mineralization,synergizing with osteogenic media supplements,showcasing the potential of adenosine for treating critical bone defects and metabolic disorders.This study high-lights the efficacy of a polymeric microparticle-based delivery system,offering novel strategies for bone repair.Unveiling adenosine’s roles and associated signalling pathways advances our comprehension of molecular mech-anisms steering bone regeneration,propelling innovative biomaterial,combined with metabolites,approaches for clinical use.

关 键 词：Adenosine release Osteogenic signalling pathways Human mesenchymal stromal cells Bone regeneration 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]