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Regulation of Smooth Muscle Actin Expression and Contraction in Adult Human Mesenchymal Stem Cells

https://doi.org/10.1006/excr.2002.5561Get rights and content

Abstract

Prior studies have demonstrated the expression of a contractile actin isoform, α-smooth muscle actin, in bone marrow stromal cells. One objective of the current study was to correlate contractility with α-smooth muscle actin expression in human bone marrow stroma-derived mesenchymal stem cells. A second objective was to determine the effects of transforming growth factor-β1, platelet derived growth factor-BB, and a microfilament-modifying agent on α-smooth muscle actin expression and α-smooth muscle actin-enabled contraction. Adult human bone marrow stromal cells were passaged in monolayer and their inducibility to chondrocytic, osteoblastic, and adipogenic phenotypes was demonstrated. Western blot analysis was employed along with densitometry to quantify the α-smooth muscle actin content of the cells and their contractility was evaluated by their contraction of a type I collagen–glycosaminoglycan sponge-like matrix into which they were seeded. Transforming growth factor-β1 (1 ng/ml) significantly increased and platelet-derived growth factor-BB (10 ng/ml) decreased α-smooth muscle actin expression and the contractility of the cells. Cytochalasin D also blocked cell contraction. There was a notably high correlation of cell-mediated contraction normalized to the DNA content of the matrices with α-smooth muscle actin content of the cells by linear regression analysis (R2 = 0.88). These findings lay the groundwork for considering the role of α-smooth muscle actin-enabled contraction in mesenchymal stem cells and in their connective tissue cell progeny.

References (58)

  • C. Menard et al.

    Contractile behavior of smooth muscle actin-containing osteoblasts in collagen–GAG matrices in vitro: Implant-related cell contraction

    Biomaterials

    (2000)
  • J. Premdas et al.

    The presence of smooth muscle actin in fibroblasts in the torn human rotator cuff

    J. Orthop. Res.

    (2001)
  • A.A. Comut et al.

    Association of fibroblast orientation around titanium in vitro with expression of a muscle actin

    Biomaterials

    (2000)
  • S. Nehrer et al.

    Matrix collagen type and pore size influence behavior of seeded canine chondrocytes

    Biomaterials

    (1997)
  • C.R. Lee et al.

    The effects of cross-linking of collagen–glycosaminoglycan scaffolds on compressive stiffness, chondrocyte-mediated contraction, proliferation and biosynthesis

    Biomaterials

    (2001)
  • T.D. Allen et al.

    The contraction of collagen matrices by dermal fibroblasts

    J. Ultrastruct. Res.

    (1983)
  • T. Nishiyama et al.

    Quantitative evaluation of the factors affecting the process of fibroblast-mediated collagen gel contraction by separating the process into three phases

    Collagen Rel. Res.

    (1988)
  • M.B. Vaughan et al.

    Transforming growth factor-beta1 promotes the morphological and functional differentiation of the myofibroblast

    Exp. Cell Res.

    (2000)
  • A.J. Friedenstein et al.

    Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo

    Transplantation

    (1974)
  • T.M. Dexter et al.

    Conditions controlling the proliferation of haemopoietic stem cells in vitro

    J. Cell Physiol.

    (1977)
  • M.F. Pittenger et al.

    Multilineage potential of adult human mesenchymal stem cells

    Science

    (1999)
  • A.I. Caplan

    Mesenchymal stem cells

    J. Orthop. Res.

    (1991)
  • D.J. Prockop

    Marrow stromal cells as stem cells for nonhematopoietic tissues

    Science

    (1997)
  • A.J. Friedenstein et al.

    Fibroblast precursors in normal and irradiated mouse hematopoietic organs

    Exp. Hematol.

    (1976)
  • D. Cai et al.

    Lapine and canine bone marrow stromal cells contain smooth muscle actin and contract a collagen–glycosaminoglycan matrix

    Tissue Eng.

    (2001)
  • P. Charbord et al.

    The cytoskeleton of stromal cells from human bone marrow cultures resembles that of cultured smooth muscle cells

    Exp. Hematol.

    (1990)
  • E. Bonanno et al.

    Homogeneous stromal cell population from normal human adult bone marrow expressing α-smooth muscle actin filaments

    Lab. Invest.

    (1994)
  • J. Li et al.

    Nontransformed colony-derived stromal cell lines from normal human marrows. II. Phenotypic characterization and differentiation pathway

    Exp. Hematol.

    (1995)
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    1

    Current address: Department of Trauma Surgery, Clinics of the University of Regensburg, Regensburg, Germany.

    2

    To whom correspondence and reprint requests should be addressed at Department of Orthopedic Surgery, MRB 106, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. Fax: (617) 732-6705. E-mail: [email protected].

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