Abstract
Mechanical stimulation affects growth and differentiation of stem cells. This may be used to guide lineage-specific cell fate decisions and therefore opens fascinating opportunities for stem cell biology and regenerative medicine. Several studies demonstrated functional and molecular effects of mechanical stimulation but on first sight these results often appear to be inconsistent. Comparison of such studies is hampered by a multitude of relevant parameters that act in concert. There are notorious differences between species, cell types, and culture conditions. Furthermore, the utilized culture substrates have complex features, such as surface chemistry, elasticity, and topography. Cell culture substrates can vary from simple, flat materials to complex 3D scaffolds. Last but not least, mechanical forces can be applied with different frequency, amplitude, and strength. It is therefore a prerequisite to take all these parameters into consideration when ascribing their specific functional relevance—and to only modulate one parameter at the time if the relevance of this parameter is addressed. Such research questions can only be investigated by interdisciplinary cooperation. In this review, we focus particularly on mesenchymal stem cells and pluripotent stem cells to discuss relevant parameters that contribute to the kaleidoscope of mechanical stimulation of stem cells.
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References
Macqueen L, Sun Y, Simmons CA (2013) Mesenchymal stem cell mechanobiology and emerging experimental platforms. J R Soc Interface 10(84):20130179
Vining KH, Mooney DJ (2017) Mechanical forces direct stem cell behaviour in development and regeneration. Nat Rev Mol Cell Biol 18(12):728–742
Rosenbaum AJ, Grande DA, Dines JS (2008) The use of mesenchymal stem cells in tissue engineering: a global assessment. Organogenesis 4(1):23–27
Ho AD, Wagner W, Franke W (2008) Heterogeneity of mesenchymal stromal cell preparations. Cytotherapy 10(4):320–330
Neuss S, Apel C, Buttler P, Denecke B, Dhanasingh A, Ding X, Grafahrend D, Groger A, Hemmrich K, Herr A, Jahnen-Dechent W, Mastitskaya S, Perez-Bouza A, Rosewick S, Salber J, Woltje M, Zenke M (2008) Assessment of stem cell/biomaterial combinations for stem cell-based tissue engineering. Biomaterials 29(3):302–313
Phinney DG, Kopen G, Righter W, Webster S, Tremain N, Prockop DJ (1999) Donor variation in the growth properties and osteogenic potential of human marrow stromal cells. J Cell Biochem 75(3):424–436
Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U, Blake J, Schwager C, Eckstein V, Ansorge W, Ho AD (2005) Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 33(11):1402–1416
Wagner W, Ho AD, Zenke M (2010) Different facets of aging in human mesenchymal stem cells. Tissue Eng Part B Rev 16(4):445–453
De Almeida DC, Ferreira MR, Franzen J, Weidner CI, Frobel J, Zenke M, Costa IG, Wagner W (2016) Epigenetic classification of human mesenchymal stromal cells. Stem Cell Rep 6(2):168–175
Wray J, Kalkan T, Smith AG (2010) The ground state of pluripotency. Biochem Soc Trans 38(4):1027–1032
Koch CM, Reck K, Shao K, Lin Q, Joussen S, Ziegler P, Walenda G, Drescher W, Opalka B, May T, Brummendorf T, Zenke M, Saric T, Wagner W (2013) Pluripotent stem cells escape from senescence-associated DNA methylation changes. Genome Res 23(2):248–259
Weidner CI, Lin Q, Koch CM, Eisele L, Beier F, Ziegler P, Bauerschlag DO, Jockel KH, Erbel R, Muhleisen TW, Zenke M, Brummendorf TH, Wagner W (2014) Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol 15(2):R24
Shao Y, Sang J, Fu J (2015) On human pluripotent stem cell control: the rise of 3D bioengineering and mechanobiology. Biomaterials 52:26–43
Ren G, Su J, Zhang L, Zhao X, Ling W, L’huillie A, Zhang J, Lu Y, Roberts AI, Ji W, Zhang H, Rabson AB, Shi Y (2009) Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells 27(8):1954–1962
Yu J, Thomson JA (2008) Pluripotent stem cell lines. Genes Dev 22(15):1987–1997
Lund P, Pilgaard L, Duroux M, Fink T, Zachar V (2009) Effect of growth media and serum replacements on the proliferation and differentiation of adipose-derived stem cells. Cytotherapy 11(2):189–197
Prakash Bangalore M, Adhikarla S, Mukherjee O, Panicker MM (2017) Genotoxic effects of culture media on human pluripotent stem cells. Sci Rep 7:42222
Anderson DG, Levenberg S, Langer R (2004) Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells. Nat Biotechnol 22(7):863–866
Anderson DG, Putnam D, Lavik EB, Mahmood TA, Langer R (2005) Biomaterial microarrays: rapid, microscale screening of polymer-cell interaction. Biomaterials 26(23):4892–4897
Flaim CJ, Chien S, Bhatia SN (2005) An extracellular matrix microarray for probing cellular differentiation. Nat Methods 2(2):119–125
Hammad M, Rao W, Smith JG, Anderson DG, Langer R, Young LE, Barrett DA, Davies MC, Denning C, Alexander MR (2016) Identification of polymer surface adsorbed proteins implicated in pluripotent human embryonic stem cell expansion. Biomater Sci 4(9):1381–1391
Epa VC, Yang J, Mei Y, Hook AL, Langer R, Anderson DG, Davies MC, Alexander MR, Winkler DA (2012) Modelling human embryoid body cell adhesion to a combinatorial library of polymer surfaces. J Mater Chem 22(39):20902–20906
Hemeda H, Giebel B, Wagner W (2014) Evaluation of human platelet lysate versus fetal bovine serum for culture of mesenchymal stromal cells. Cytotherapy 16(2):170–180
Mei Y, Saha K, Bogatyrev SR, Yang J, Hook AL, Kalcioglu ZI, Cho SW, Mitalipova M, Pyzocha N, Rojas F, Van Vliet KJ, Davies MC, Alexander MR, Langer R, Jaenisch R, Anderson DG (2010) Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells. Nat Mater 9(9):768–778
Hoss M, Apel C, Dhanasingh A, Suschek CV, Hemmrich K, Salber J, Zenke M, Neuss S (2013) Integrin alpha4 impacts on differential adhesion of preadipocytes and stem cells on synthetic polymers. J Tissue Eng Regen Med 7(4):312–323
Guilak F, Cohen DM, Estes BT, Gimble JM, Liedtke W, Chen CS (2009) Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell 5(1):17–26
Li Y, Kilian KA (2015) Bridging the Gap: from 2D Cell Culture to 3D Microengineered Extracellular Matrices. Adv Healthc Mater 4(18):2780–2796
Chan BP, Leong KW (2008) Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur Spine J 17(Suppl 4):467–479
El-Sherbiny IM (2013) Yacoub MH (2013) Hydrogel scaffolds for tissue engineering: progress and challenges. Glob Cardiol Sci Pract 3:316–342
Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA (2009) Hydrogels in regenerative medicine. Adv Mater 21(32–33):3307–3329
Rice JJ, Martino MM, De Laporte L, Tortelli F, Briquez PS, Hubbell JA (2013) Engineering the regenerative microenvironment with biomaterials. Adv Healthc Mater 2(1):57–71
Discher DE, Janmey P, Wang YL (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310(5751):1139–1143
Mckinnon DD, Domaille DW, Cha JN, Anseth KS (2014) Biophysically defined and cytocompatible covalently adaptable networks as viscoelastic 3D cell culture systems. Adv Mater 26(6):865–872
Kouwer PH, Koepf M, Le Sage VA, Jaspers M, Van Buul AM, Eksteen-Akeroyd ZH, Woltinge T, Schwartz E, Kitto HJ, Hoogenboom R, Picken SJ, Nolte RJ, Mendes E, Rowan AE (2013) Responsive biomimetic networks from polyisocyanopeptide hydrogels. Nature 493(7434):651–655
Baker BM, Trappmann B, Wang WY, Sakar MS, Kim IL, Shenoy VB, Burdick JA, Chen CS (2015) Cell-mediated fibre recruitment drives extracellular matrix mechanosensing in engineered fibrillar microenvironments. Nat Mater 14(12):1262–1268
Patterson J, Hubbell JA (2010) Enhanced proteolytic degradation of molecularly engineered PEG hydrogels in response to MMP-1 and MMP-2. Biomaterials 31(30):7836–7845
Dadsetan M, Hefferan TE, Szatkowski JP, Mishra PK, Macura SI, Lu L, Yaszemski MJ (2008) Effect of hydrogel porosity on marrow stromal cell phenotypic expression. Biomaterials 29(14):2193–2202
Murphy CM, O’brien FJ (2010) Understanding the effect of mean pore size on cell activity in collagen-glycosaminoglycan scaffolds. Cell Adhes Migr 4(3):377–381
Keaveny TM, Morgan EF, Niebur GL, Yeh OC (2001) Biomechanics of trabecular bone. Annu Rev Biomed Eng 3:307–333
Lo YP, Liu YS, Rimando MG, Ho JH, Lin KH, Lee OK (2016) Three-dimensional spherical spatial boundary conditions differentially regulate osteogenic differentiation of mesenchymal stromal cells. Sci Rep 6:21253
Chen H, Huang X, Zhang M, Damanik F, Baker MB, Leferink A, Yuan H, Truckenmuller R, Van Blitterswijk C, Moroni L (2017) Tailoring surface nanoroughness of electrospun scaffolds for skeletal tissue engineering. Acta Biomater 59:82–93
Chen H, Malheiro A, Van Blitterswijk C, Mota C, Wieringa PA, Moroni L (2017) Direct writing electrospinning of scaffolds with multidimensional fiber architecture for hierarchical tissue engineering. ACS Appl Mater Interfaces 9(44):38187–38200
Neves SC, Mota C, Longoni A, Barrias CC, Granja PL, Moroni L (2016) Additive manufactured polymeric 3D scaffolds with tailored surface topography influence mesenchymal stromal cells activity. Biofabrication 8(2):025012
Schellenberg A, Joussen S, Moser K, Hampe N, Hersch N, Hemeda H, Schnitker J, Denecke B, Lin Q, Pallua N, Zenke M, Merkel R, Hoffmann B, Wagner W (2014) Matrix elasticity, replicative senescence and DNA methylation patterns of mesenchymal stem cells. Biomaterials 35(24):6351–6358
Omidinia-Anarkoli A, Boesveld S, Tuvshindorj U, Rose JC, Haraszti T, De Laporte L (2017) An injectable hybrid hydrogel with oriented short fibers induces unidirectional growth of functional nerve cells. Small 13(36):1702207
Zhang S, Liu X, Barreto-Ortiz SF, Yu Y, Ginn BP, Desantis NA, Hutton DL, Grayson WL, Cui FZ, Korgel BA, Gerecht S, Mao HQ (2014) Creating polymer hydrogel microfibres with internal alignment via electrical and mechanical stretching. Biomaterials 35(10):3243–3251
Prasopthum A, Shakesheff KM, Yang J (2018) Direct three-dimensional printing of polymeric scaffolds with nanofibrous topography. Biofabrication 10(2):025002
Xu R, Taskin MB, Rubert M, Seliktar D, Besenbacher F, Chen M (2015) hiPS-MSCs differentiation towards fibroblasts on a 3D ECM mimicking scaffold. Sci Rep 5:8480
Taskin MB, Xu R, Gregersen H, Nygaard JV, Besenbacher F, Chen M (2016) Three-dimensional polydopamine functionalized coiled microfibrous scaffolds enhance human mesenchymal stem cells colonization and mild myofibroblastic differentiation. ACS Appl Mater Interfaces 8(25):15864–15873
Gilbert PM, Havenstrite KL, Magnusson KE, Sacco A, Leonardi NA, Kraft P, Nguyen NK, Thrun S, Lutolf MP, Blau HM (2010) Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture. Science 329(5995):1078–1081
Discher DE, Mooney DJ, Zandstra PW (2009) Growth factors, matrices, and forces combine and control stem cells. Science 324(5935):1673–1677
Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689
Chen YM, Chen LH, Li MP, Li HF, Higuchi A, Kumar SS, Ling QD, Alarfaj AA, Munusamy MA, Chang Y, Benelli G, Murugan K, Umezawa A (2017) Xeno-free culture of human pluripotent stem cells on oligopeptide-grafted hydrogels with various molecular designs. Sci Rep 7:45146
Zhang R, Mjoseng HK, Hoeve MA, Bauer NG, Pells S, Besseling R, Velugotla S, Tourniaire G, Kishen RE, Tsenkina Y, Armit C, Duffy CR, Helfen M, Edenhofer F, De Sousa PA, Bradley M (2013) A thermoresponsive and chemically defined hydrogel for long-term culture of human embryonic stem cells. Nat Commun 4:1335
Caiazzo M, Okawa Y, Ranga A, Piersigilli A, Tabata Y, Lutolf MP (2016) Defined three-dimensional microenvironments boost induction of pluripotency. Nat Mater 15(3):344–352
Dixon JE, Shah DA, Rogers C, Hall S, Weston N, Parmenter CD, Mcnally D, Denning C, Shakesheff KM (2014) Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation. Proc Natl Acad Sci USA 111(15):5580–5585
Zhu R, Blazeski A, Poon E, Costa KD, Tung L, Boheler KR (2014) Physical developmental cues for the maturation of human pluripotent stem cell-derived cardiomyocytes. Stem Cell Res Ther 5(5):117
Pellett S, Schwartz MP, Tepp WH, Josephson R, Scherf JM, Pier CL, Thomson JA, Murphy WL, Johnson EA (2015) Human induced pluripotent stem cell derived neuronal cells cultured on chemically-defined hydrogels for sensitive in vitro detection of botulinum neurotoxin. Sci Rep 5:14566
Zhang ZN, Freitas BC, Qian H, Lux J, Acab A, Trujillo CA, Herai RH, Nguyen Huu VA, Wen JH, Joshi-Barr S, Karpiak JV, Engler AJ, Fu XD, Muotri AR, Almutairi A (2016) Layered hydrogels accelerate iPSC-derived neuronal maturation and reveal migration defects caused by MeCP2 dysfunction. Proc Natl Acad Sci USA 113(12):3185–3190
Wang B, Jakus AE, Baptista PM, Soker S, Soto-Gutierrez A, Abecassis MM, Shah RN, Wertheim JA (2016) Functional maturation of induced pluripotent stem cell hepatocytes in extracellular matrix-a comparative analysis of bioartificial liver microenvironments. Stem Cells Transl Med 5(9):1257–1267
Goetzke R, Franzen J, Ostrowska A, Vogt M, Blaeser A, Klein G, Rath B, Fischer H, Zenke M, Wagner W (2018) Does soft really matter? Differentiation of induced pluripotent stem cells into mesenchymal stromal cells is not influenced by soft hydrogels. Biomaterials 156:147–158
Walenda G, Hemeda H, Schneider RK, Merkel R, Hoffmann B, Wagner W (2012) Human platelet lysate gel provides a novel 3D-matrix for enhanced culture expansion of mesenchymal stromal cells. Tissue Eng Part C. Methods 18(12):924–934
Gobaa S, Hoehnel S, Roccio M, Negro A, Kobel S, Lutolf MP (2011) Artificial niche microarrays for probing single stem cell fate in high throughput. Nat Methods 8(11):949–955
Ranga A, Gobaa S, Okawa Y, Mosiewicz K, Negro A, Lutolf MP (2014) 3D niche microarrays for systems-level analyses of cell fate. Nat Commun 5:4324
Chaudhuri O, Gu L, Darnell M, Klumpers D, Bencherif SA, Weaver JC, Huebsch N, Mooney DJ (2015) Substrate stress relaxation regulates cell spreading. Nat Commun 6:6364
Huebsch N, Arany PR, Mao AS, Shvartsman D, Ali OA, Bencherif SA, Rivera-Feliciano J, Mooney DJ (2010) Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nat Mater 9(6):518–526
Chaudhuri O, Gu L, Klumpers D, Darnell M, Bencherif SA, Weaver JC, Huebsch N, Lee HP, Lippens E, Duda GN, Mooney DJ (2016) Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat Mater 15(3):326–334
Talele NP, Fradette J, Davies JE, Kapus A, Hinz B (2015) Expression of alpha-smooth muscle actin determines the fate of mesenchymal stromal cells. Stem Cell Reports 4(6):1016–1030
Ishihara S, Inman DR, Li WJ, Ponik SM, Keely PJ (2017) Mechano-signal transduction in mesenchymal stem cells induces prosaposin secretion to drive the proliferation of breast cancer cells. Cancer Res 77(22):6179–6189
Trappmann B, Gautrot JE, Connelly JT, Strange DG, Li Y, Oyen ML, Cohen Stuart MA, Boehm H, Li B, Vogel V, Spatz JP, Watt FM, Huck WT (2012) Extracellular-matrix tethering regulates stem-cell fate. Nat Mater 11(7):642–649
Abagnale G, Steger M, Nguyen VH, Hersch N, Sechi A, Joussen S, Denecke B, Merkel R, Hoffmann B, Dreser A, Schnakenberg U, Gillner A, Wagner W (2015) Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages. Biomaterials 61:316–326
Murphy WL, Mcdevitt TC, Engler AJ (2014) Materials as stem cell regulators. Nat Mater 13(6):547–557
Kilian KA, Bugarija B, Lahn BT, Mrksich M (2010) Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci USA 107(11):4872–4877
Mcbeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6(4):483–495
Werner M, Blanquer SB, Haimi SP, Korus G, Dunlop JW, Duda GN, Grijpma DW, Petersen A (2017) Surface curvature differentially regulates stem cell migration and differentiation via altered attachment morphology and nuclear deformation. Adv Sci (Weinh) 4(2):1600347
Hulshof FFB, Zhao Y, Vasilevich A, Beijer NRM, De Boer M, Papenburg BJ, Van Blitterswijk C, Stamatialis D, De Boer J (2017) NanoTopoChip: high-throughput nanotopographical cell instruction. Acta Biomater 62:188–198
Markert LD, Lovmand J, Foss M, Lauridsen RH, Lovmand M, Fuchtbauer EM, Fuchtbauer A, Wertz K, Besenbacher F, Pedersen FS, Duch M (2009) Identification of distinct topographical surface microstructures favoring either undifferentiated expansion or differentiation of murine embryonic stem cells. Stem Cells Dev 18(9):1331–1342
Unadkat HV, Hulsman M, Cornelissen K, Papenburg BJ, Truckenmuller RK, Carpenter AE, Wessling M, Post GF, Uetz M, Reinders MJ, Stamatialis D, Van Blitterswijk CA, De Boer J (2011) An algorithm-based topographical biomaterials library to instruct cell fate. Proc Natl Acad Sci USA 108(40):16565–16570
Kuo SW, Lin HI, Ho JH, Shih YR, Chen HF, Yen TJ, Lee OK (2012) Regulation of the fate of human mesenchymal stem cells by mechanical and stereo-topographical cues provided by silicon nanowires. Biomaterials 33(20):5013–5022
Oh S, Brammer KS, Li YS, Teng D, Engler AJ, Chien S, Jin S (2009) Stem cell fate dictated solely by altered nanotube dimension. Proc Natl Acad Sci USA 106(7):2130–2135
Park J, Bauer S, Von Der MK, Schmuki P (2007) Nanosize and vitality: tiO2 nanotube diameter directs cell fate. Nano Lett 7(6):1686–1691
Zhou Q, Castaneda Ocampo O, Guimaraes CF, Kuhn PT, Van Kooten TG, Van Rijn P (2017) Screening platform for cell contact guidance based on inorganic biomaterial micro/nanotopographical gradients. ACS Appl Mater Interfaces 9(37):31433–31445
Abagnale G, Sechi A, Steger M, Zhou Q, Kuo CC, Aydin G, Schalla C, Muller-Newen G, Zenke M, Costa IG, Van Rijn P, Gillner A, Wagner W (2017) Surface topography guides morphology and spatial patterning of induced pluripotent stem cell colonies. Stem Cell Rep 9(2):654–666
Peerani R, Rao BM, Bauwens C, Yin T, Wood GA, Nagy A, Kumacheva E, Zandstra PW (2007) Niche-mediated control of human embryonic stem cell self-renewal and differentiation. EMBO J 26(22):4744–4755
Arnold M, Cavalcanti-Adam EA, Glass R, Blummel J, Eck W, Kantlehner M, Kessler H, Spatz JP (2004) Activation of integrin function by nanopatterned adhesive interfaces. ChemPhysChem 5(3):383–388
Cavalcanti-Adam EA, Volberg T, Micoulet A, Kessler H, Geiger B, Spatz JP (2007) Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. Biophys J 92(8):2964–2974
Altrock E, Muth CA, Klein G, Spatz JP, Lee-Thedieck C (2012) The significance of integrin ligand nanopatterning on lipid raft clustering in hematopoietic stem cells. Biomaterials 33(11):3107–3118
Lee KY, Alsberg E, Hsiong S, Comisar W, Linderman J, Ziff R, Mooney D (2004) Nanoscale adhesion ligand organization regulates osteoblast proliferation and differentiation. Nano Lett 4(8):1501–1506
Frith JE, Mills RJ, Cooper-White JJ (2012) Lateral spacing of adhesion peptides influences human mesenchymal stem cell behaviour. J Cell Sci 125(Pt 2):317–327
Wolff J (1892) Das Gesetz der Transformation der Knochen. Verlag von August Hirschwald
Lanyon LE, Rubin CT (1984) Static vs dynamic loads as an influence on bone remodelling. J Biomech 17(12):897–905
Mosley JR, Lanyon LE (1998) Strain rate as a controlling influence on adaptive modeling in response to dynamic loading of the ulna in growing male rats. Bone 23(4):313–318
O’connor JA, Lanyon LE, Macfie H (1982) The influence of strain rate on adaptive bone remodelling. J Biomech 15(10):767–781
Bullard RW (1972) Physiological problems of space travel. Annu Rev Physiol 34:205–234
Grimm D, Grosse J, Wehland M, Mann V, Reseland JE, Sundaresan A, Corydon TJ (2016) The impact of microgravity on bone in humans. Bone 87:44–56
Pan Z, Yang J, Guo C, Shi D, Shen D, Zheng Q, Chen R, Xu Y, Xi Y, Wang J (2008) Effects of hindlimb unloading on ex vivo growth and osteogenic/adipogenic potentials of bone marrow-derived mesenchymal stem cells in rats. Stem Cells Dev 17(4):795–804
Sheyn D, Pelled G, Netanely D, Domany E, Gazit D (2010) The effect of simulated microgravity on human mesenchymal stem cells cultured in an osteogenic differentiation system: a bioinformatics study. Tissue Eng Part A 16(11):3403–3412
Govoni M, Lotti F, Biagiotti L, Lannocca M, Pasquinelli G, Valente S, Muscari C, Bonafe F, Caldarera CM, Guarnieri C, Cavalcanti S, Giordano E (2014) An innovative stand-alone bioreactor for the highly reproducible transfer of cyclic mechanical stretch to stem cells cultured in a 3D scaffold. J Tissue Eng Regen Med 8(10):787–793
Xu B, Song G, Ju Y, Li X, Song Y, Watanabe S (2012) RhoA/ROCK, cytoskeletal dynamics, and focal adhesion kinase are required for mechanical stretch-induced tenogenic differentiation of human mesenchymal stem cells. J Cell Physiol 227(6):2722–2729
Wei F, Liu D, Feng C, Zhang F, Yang S, Hu Y, Ding G, Wang S (2015) microRNA-21 mediates stretch-induced osteogenic differentiation in human periodontal ligament stem cells. Stem Cells Dev 24(3):312–319
Zhu Z, Gan X, Fan H, Yu H (2015) Mechanical stretch endows mesenchymal stem cells stronger angiogenic and anti-apoptotic capacities via NFkappaB activation. Biochem Biophys Res Commun 468(4):601–605
Mihic A, Li J, Miyagi Y, Gagliardi M, Li SH, Zu J, Weisel RD, Keller G, Li RK (2014) The effect of cyclic stretch on maturation and 3D tissue formation of human embryonic stem cell-derived cardiomyocytes. Biomaterials 35(9):2798–2808
Zhang W, Kong CW, Tong MH, Chooi WH, Huang N, Li RA, Chan BP (2017) Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in 3D collagen matrix: effects of niche cell supplementation and mechanical stimulation. Acta Biomater 49:204–217
Ravichandran A, Lim J, Chong MSK, Wen F, Liu Y, Pillay YT, Chan JKY, Teoh SH (2017) In vitro cyclic compressive loads potentiate early osteogenic events in engineered bone tissue. J Biomed Mater Res B Appl Biomater 105(8):2366–2375
Horner CB, Hirota K, Liu J, Maldonado M, Hyle Park B, Nam J (2016) Magnitude-dependent and inversely-related osteogenic/chondrogenic differentiation of human mesenchymal stem cells under dynamic compressive strain. J Tissue Eng Regen Med 12(2):e637–e647
Jung Y, Kim SH, Kim YH, Kim SH (2009) The effects of dynamic and three-dimensional environments on chondrogenic differentiation of bone marrow stromal cells. Biomed Mater 4(5):055009
Terraciano V, Hwang N, Moroni L, Park HB, Zhang Z, Mizrahi J, Seliktar D, Elisseeff J (2007) Differential response of adult and embryonic mesenchymal progenitor cells to mechanical compression in hydrogels. Stem Cells 25(11):2730–2738
Appelman TP, Mizrahi J, Elisseeff JH, Seliktar D (2009) The differential effect of scaffold composition and architecture on chondrocyte response to mechanical stimulation. Biomaterials 30(4):518–525
Appelman TP, Mizrahi J, Elisseeff JH, Seliktar D (2011) The influence of biological motifs and dynamic mechanical stimulation in hydrogel scaffold systems on the phenotype of chondrocytes. Biomaterials 32(6):1508–1516
Glossop JR, Cartmell SH (2009) Effect of fluid flow-induced shear stress on human mesenchymal stem cells: differential gene expression of IL1B and MAP3K8 in MAPK signaling. Gene Expr Patterns 9(5):381–388
Yeatts AB, Choquette DT (1830) Fisher JP (2013) Bioreactors to influence stem cell fate: augmentation of mesenchymal stem cell signaling pathways via dynamic culture systems. Biochim Biophys Acta 2:2470–2480
Stavenschi E, Labour MN, Hoey DA (2017) Oscillatory fluid flow induces the osteogenic lineage commitment of mesenchymal stem cells: the effect of shear stress magnitude, frequency, and duration. J Biomech 55:99–106
Ohtani-Kaneko R, Sato K, Tsutiya A, Nakagawa Y, Hashizume K, Tazawa H (2017) Characterisation of human induced pluripotent stem cell-derived endothelial cells under shear stress using an easy-to-use microfluidic cell culture system. Biomed Microdevices 19(4):91
Sivarapatna A, Ghaedi M, Le AV, Mendez JJ, Qyang Y, Niklason LE (2015) Arterial specification of endothelial cells derived from human induced pluripotent stem cells in a biomimetic flow bioreactor. Biomaterials 53:621–633
Hoey DA, Tormey S, Ramcharan S, O’brien FJ, Jacobs CR (2012) Primary cilia-mediated mechanotransduction in human mesenchymal stem cells. Stem Cells 30(11):2561–2570
Singla V, Reiter JF (2006) The primary cilium as the cell’s antenna: signaling at a sensory organelle. Science 313(5787):629–633
Coughlin TR, Voisin M, Schaffler MB, Niebur GL, Mcnamara LM (2015) Primary cilia exist in a small fraction of cells in trabecular bone and marrow. Calcif Tissue Int 96(1):65–72
Chen JC, Hoey DA, Chua M, Bellon R, Jacobs CR (2016) Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism. FASEB J 30(4):1504–1511
Tse JR, Engler AJ (2011) Stiffness gradients mimicking in vivo tissue variation regulate mesenchymal stem cell fate. PLoS ONE 6(1):e15978
Yang C, Tibbitt MW, Basta L, Anseth KS (2014) Mechanical memory and dosing influence stem cell fate. Nat Mater 13(6):645–652
Guvendiren M, Burdick JA (2012) Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics. Nat Commun 3:792
Hendrikson WJ, Rouwkema J, Clementi F, Van Blitterswijk CA, Fare S, Moroni L (2017) Towards 4D printed scaffolds for tissue engineering: exploiting 3D shape memory polymers to deliver time-controlled stimulus on cultured cells. Biofabrication 9(3):031001
Rammensee S, Kang MS, Georgiou K, Kumar S, Schaffer DV (2017) Dynamics of mechanosensitive neural stem cell differentiation. Stem Cells 35(2):497–506
Hamidouche Z, Fromigue O, Ringe J, Haupl T, Vaudin P, Pages JC, Srouji S, Livne E, Marie PJ (2009) Priming integrin alpha5 promotes human mesenchymal stromal cell osteoblast differentiation and osteogenesis. Proc Natl Acad Sci U S A 106(44):18587–18591
Shih YR, Tseng KF, Lai HY, Lin CH, Lee OK (2011) Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells. J Bone Miner Res 26(4):730–738
Yu H, Lui YS, Xiong S, Leong WS, Wen F, Nurkahfianto H, Rana S, Leong DT, Ng KW, Tan LP (2013) Insights into the role of focal adhesion modulation in myogenic differentiation of human mesenchymal stem cells. Stem Cells Dev 22(1):136–147
Du J, Chen X, Liang X, Zhang G, Xu J, He L, Zhan Q, Feng XQ, Chien S, Yang C (2011) Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity. Proc Natl Acad Sci U S A 108(23):9466–9471
Hwang JH, Lee DH, Byun MR, Kim AR, Kim KM, Park JI, Oh HT, Hwang ES, Lee KB, Hong JH (2017) Nanotopological plate stimulates osteogenic differentiation through TAZ activation. Sci Rep 7(1):3632
Sen B, Guilluy C, Xie Z, Case N, Styner M, Thomas J, Oguz I, Rubin C, Burridge K, Rubin J (2011) Mechanically induced focal adhesion assembly amplifies anti-adipogenic pathways in mesenchymal stem cells. Stem Cells 29(11):1829–1836
Teramura T, Takehara T, Onodera Y, Nakagawa K, Hamanishi C, Fukuda K (2012) Mechanical stimulation of cyclic tensile strain induces reduction of pluripotent related gene expressions via activation of Rho/ROCK and subsequent decreasing of AKT phosphorylation in human induced pluripotent stem cells. Biochem Biophys Res Commun 417(2):836–841
Sen B, Xie Z, Case N, Thompson WR, Uzer G, Styner M, Rubin J (2014) mTORC2 regulates mechanically induced cytoskeletal reorganization and lineage selection in marrow-derived mesenchymal stem cells. J Bone Miner Res 29(1):78–89
Zhang P, Wu Y, Jiang Z, Jiang L, Fang B (2012) Osteogenic response of mesenchymal stem cells to continuous mechanical strain is dependent on ERK1/2-Runx2 signaling. Int J Mol Med 29(6):1083–1089
Hoffman LM, Jensen CC, Chaturvedi A, Yoshigi M, Beckerle MC (2012) Stretch-induced actin remodeling requires targeting of zyxin to stress fibers and recruitment of actin regulators. Mol Biol Cell 23(10):1846–1859
Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, Zanconato F, Le DJ, Forcato M, Bicciato S, Elvassore N, Piccolo S (2011) Role of YAP/TAZ in mechanotransduction. Nature 474(7350):179–183
Sathe AR, Shivashankar GV, Sheetz MP (2016) Nuclear transport of paxillin depends on focal adhesion dynamics and FAT domains. J Cell Sci 129(10):1981–1988
Sabra H, Brunner M, Mandati V, Wehrle-Haller B, Lallemand D, Ribba AS, Chevalier G, Guardiola P, Block MR, Bouvard D (2017) beta1 integrin-dependent Rac/group I PAK signaling mediates YAP activation of Yes-associated protein 1 (YAP1) via NF2/merlin. J Biol Chem 292(47):19179–19197
Lammerding J, Fong LG, Ji JY, Reue K, Stewart CL, Young SG, Lee RT (2006) Lamins A and C but not lamin B1 regulate nuclear mechanics. J Biol Chem 281(35):25768–25780
Swift J, Ivanovska IL, Buxboim A, Harada T, Dingal PC, Pinter J, Pajerowski JD, Spinler KR, Shin JW, Tewari M, Rehfeldt F, Speicher DW, Discher DE (2013) Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341(6149):1240104
Frobel J, Hemeda H, Lenz M, Abagnale G, Joussen S, Denecke B, Saric T, Zenke M, Wagner W (2014) Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells. Stem Cell Reports 3(3):414–422
Acknowledgements
This work was supported by the German Ministry of Education and Research (WW: OBELICS, 01KU1402B), by the RWTH Aachen University within ERS Seed Fund projects (WW and RG: OPSF433; SN: OPBF071), and by the Interdisciplinary Center for Clinical Research (IZKF) within the faculty of Medicine at the RWTH Aachen University (WW: T11-2).
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Goetzke, R., Sechi, A., De Laporte, L. et al. Why the impact of mechanical stimuli on stem cells remains a challenge. Cell. Mol. Life Sci. 75, 3297–3312 (2018). https://doi.org/10.1007/s00018-018-2830-z
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DOI: https://doi.org/10.1007/s00018-018-2830-z