Low Frequency Stimulation of Stem Cells in Dynamic Culture Modulates Differentiation Pathways

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URL: https://escholarship.mcgill.ca/concern/theses/zs25xc98r

Abstract (English)

Living cells, depending on their physiological functions, are subjected to a variety of mechanical stimulation. The magnitude and frequency of such mechanical stimulation varies dramatically in different organs. Oscillatory mechanical stimulation at relatively high frequancies, as occurs in walking, respiration and circulation, is one of the most extensively studied schemes. However, the stimulation at extremely low frequencies is rarely examined. This research investigates the effects of relatively low frequency mechanical stimulation in molecular scale, on different cell types. Throughout the work presented in this document, the emphasis was on the stem cells differentiation, and primary cells dedifferentiation. The results suggested that performing extremely slow activities, namely low frequency movements, significantly affects the differentiation pathways of stem cells. In addition, it was found that slow movement of surface culture area enhances phenotypical characteristics of primary cells.

Abstract (French)

Toutes les cellules vivantes, selon leur fonctions physiologiques, sont soumises à différentes stimulations mécaniques. L'ampleur et la fréquence de ces stimulations mécaniques varies considérablement d'un organe à un autre. Les stimulations oscillantes dues notamment à la marche, la respiration et la circulation sanguine sont largement étudiées. Par contre, les travaux concernant les stimulations a très faibles fréquences sont rare. Cette recherche examine les effets sur différents types de molécules, des stimulations mécaniques à relativement basse fréquence, à l'échelle moléculaire. Tout au long du travail présenté ici, l'accent a été mis sur la différenciation des cellules souches et la dedifférenciation des cellules primaires. Les résultats suggèrent que la pratique d'activités extrêmement lentes, à savoir les mouvements à basse fréquence, affectent, de manière significative, le mécanisme de différentiation des cellules souches. En outre, il a été constaté que les mouvements lents à la surface des cultures améliorent les caractéristiques phénotypiques des cellules primaires.

Cited Works (23)

Year	Entry
2006	Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS, Deans RJ, Keating A, Prockop DJ, Horwitz EM. Minimal criteria for defining multipotent mesenchymal stromal cells: the International Society for Cellular Therapy position statement. Cytotherapy. August 2006;8(4):315-317.
2000	Brown TD. Techniques for mechanical stimulation of cells in vitro: a review. J Biomech. January 2000;33(1):3-14.
2006	Robinson JA, Chatterjee-Kishore M, Yaworsky PJ, Cullen DM, Zhao W, Li C, Kharode Y, Sauter L, Babij P, Brown EL, Hill AA, Akhter MP, Johnson ML, Recker RR, Komm BS, Bex FJ. Wnt/β-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem. October 20, 2006;281(42):31720-31728.
2005	Day TF, Guo X, Garrett-Beal L, Yang Y. Wnt/β-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell. May 2005;8(5):739-750.
2002	Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. January 11, 2002;108(1):17-29.
2005	Darling EM, Athanasiou KA. Rapid phenotypic changes in passaged articular chondrocyte subpopulations. J Orthop Res. March 2005;23(2):425-432.
2007	David V, Martin A, Lafage-Proust M-H, Malaval L, Peyroche S, Jones DB, Vico L, Guignandon A. Mechanical loading down-regulates peroxisome proliferator-activated receptor γ in bone marrow stromal cells and favors osteoblastogenesis at the expense of adipogenesis. Endocrinology. May 2007;148(5):2553-2562.
2009	Luu YK, Capilla E, Rosen CJ, Gilsanz V, Pessin JE, Judex S, Rubin CT. Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J Bone Miner Res. January 2009;24(1):50-61.
1989	Burr DB, Schaffler MB, Yang KH, Lukoschek M, Sivaneri N, Blaha JD, Radin EL. Skeletal change in response to altered strain environments: is woven bone a response to elevated strain? Bone. 1989;10(3):223-233.
2001	Rubin C, Turner AS, Bain S, Mallinckrodt C, McLeod K. Low mechanical signals strengthen long bones. Nature. August 9, 2001;412(6847):603-604.
2006	Rubin J, Rubin C, Jacobs CR. Molecular pathways mediating mechanical signaling in bone. Gene. February 15, 2006;367:1-16.
2011	Anderson DD, Chubinskaya S, Guilak F, Martin JA, Oegema TR, Olson SA, Buckwalter JA. Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J Orthop Res. June 2011;29(6):802-809.
1999	Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. April 2, 1999;284(5411):143-147.
1994	Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. NEJM. October 6, 1994;331(14):889-895.
2010	Lau E, Al-Dujaili S, Guenther A, Liu D, Wang L, You L. Effect of low-magnitude, high-frequency vibration on osteocytes in the regulation of osteoclasts. Bone. June 2010;46(6):1508-1515.
2000	Millward-Sadler SJ, Wright MO, Davies LW, Nuki G, Salter DM. Mechanotransduction via integrins and interleukin-4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes. Arthritis Rheum. September 2000;43(9):2091-2099.
1997	Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao Y-H, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. May 30, 1997;89(5):755-764.
2003	Wong M, Siegrist M, Goodwin K. Cyclic tensile strain and cyclic hydrostatic pressure differentially regulate expression of hypertrophic markers in primary chondrocytes. Bone. October 2003;33(4):685-693.
1993	Langer R, Vacanti JP. Tissue engineering. Science. May 14, 1993;260(5110):920-926.
2001	Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. December 2001;25(4):402-408.
1994	Weinbaum S, Cowin SC, Zeng Y. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech. March 1994;27(3):339-360.
2005	Hill TP, Später D, Taketo MM, Birchmeier W, Hartmann C. Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell. May 2005;8(5):727-738.
2010	Ozcivici E, Luu YK, Adler B, Qin Y-X, Rubin J, Judex S, Rubin CT. Mechanical signals as anabolic agents in bone. Nat Rev Rheumatol. January 2010;6(1):50-59.