Low intensity mechanical signals promote proliferation in a cell-specific manner:Tailoring a non-drug strategy to enhance biomanufacturing yields  

作　　者：M.Ete Chan Christopher Ashdown Lia Strait Sishir Pasumarthy Abdullah Hassan Steven Crimarco Chanpreet Singh Vihitaben S.Patel Gabriel Pagnotti Omor Khan Gunes Uzer Clinton T.Rubin 

机构地区：[1]Department of Biomedical Engineering,College of Engineering and Applied Sciences,Renaissance School of Medicine,Stony Brook University,Stony Brook,NY,11794-5280,USA [2]Medical Scientist Training Program,Renaissance School of Medicine,Stony Brook University,Stony Brook,NY,11794,USA [3]Department of Endocrine Neoplasia and Hormonal Disorders,MD Anderson Cancer Center,Houston,TX,77030,USA [4]Department of Mechanical and Biomedical Engineering,College of Engineering,Boise State University,Boise,ID,83725-205,USA [5]Center for Biotechnology,New York State Center for Advanced Technology in Medical Biotechnology,Stony Brook University,Stony Brook,NY,11794-5281,USA

出　　处：《Mechanobiology in Medicine》2024年第4期59-68,共10页力学生物学与医学（英文）

基　　金：supported by the Long Island Bioscience Hub funded through the NIH-Research Evaluation and Commercialization Hub(U-HL127522);the Research Foundation Technology Accelerator Fund,the Center for Biotechnology(NYSTAR)as well as grants from NIH(AG059923,P20GM109095)and NSF(1929188&2025505).

摘　　要：Biomanufacturing relies on living cells to produce biotechnology-based therapeutics,tissue engineering constructs,vaccines,and a vast range of agricultural and industrial products.With the escalating demand for these bio-based products,any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline.While these goals are primarily achieved using biological or chemical strategies,harnessing cell mechanosensitivity represents a promising–albeit less studied–physical pathway to promote bioprocessing endpoints,yet identifying which mechanical parameters influence cell activities has remained elusive.We tested the hypothesis that mechanical signals,delivered non-invasively using low-intensity vibration(LIV;<1 g,10–500 Hz),will enhance cell expansion,and determined that any unique signal configuration was not equally influential across a range of cell types.Varying frequency,intensity,duration,refractory period,and daily doses of LIV increased proliferation in Chinese Hamster Ovary(CHO)-adherent cells(t79%in 96 hr)using a particular set of LIV parameters(0.2 g,500 Hz,3-30 min/d,2 hr refractory period),yet this same mechanical input suppressed proliferation in CHO-suspension cells(-13%).Another set of LIV parameters(30 Hz,0.7 g,2-60 min/d,2 hr refractory period)however,were able to increase the proliferation of CHO-suspension cells by 210%and T-cells by 20.3%.Importantly,we also reported that T-cell response to LIV was in-part dependent upon AKT phosphorylation,as inhibiting AKT phosphorylation reduced the proliferative effect of LIV by over 60%,suggesting that suspension cells utilize mechanism(s)similar to adherent cells to sense specific LIV signals.Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids(>90%),and LIV effectively scaled up to T75 flasks.Ultimately,when LIV is tailored to the target cell population,it's highly efficient transmission acro

关 键 词：Biomanufacturing Cell proliferation Mechanical stimulation BIOMECHANICS Adherent cells Suspension cells Stem cells Vibration 

分 类 号：R318[医药卫生—生物医学工程]