Herman H. Vandenburgh

Bio: Herman H. Vandenburgh is an academic researcher from Brown University. The author has contributed to research in topics: Skeletal muscle & Myocyte. The author has an hindex of 40, co-authored 88 publications receiving 5287 citations. Previous affiliations of Herman H. Vandenburgh include Katholieke Universiteit Leuven & Harvard University.

Mechanical stimulation improves tissue-engineered human skeletal muscle

Abstract: Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

Mechanical forces and their second messengers in stimulating cell growth in vitro

Abstract: Mechanical forces play an important role in modulating the growth of a number of different tissues including skeletal muscle, smooth muscle, cardiac muscle, bone, endothelium, epithelium, and lung....

Insulin and IGF-I induce pronounced hypertrophy of skeletal myofibers in tissue culture

Abstract: Skeletal myofibers differentiated from primary avian myoblasts in tissue culture can be maintained in positive nitrogen balance in a defined serum-free medium for at least 6-7 days when embedded in a three-dimensional collagen gel matrix. Incubation of established myofiber cultures for 3-7 days with insulin (1 microM) or insulin-like growth factor I (IGF-I, 32 nM) stimulates both cell hyperplasia and myofiber hypertrophy. Mean myofiber diameter increases 71-98%. Insulin-like growth factor II stimulates cell hyperplasia but not myofiber hypertrophy. Cell growth results from a 42-62% increase in total protein synthesis and a 28-38% decrease in protein degradation. Myosin heavy-chain content increases 183-258% because of a 55% stimulation of myosin synthesis and 33-61% inhibition of degradation. Associated with myofiber hypertrophy is a 87-148% increase in the number of myofiber nuclei per unit myofiber length. The results indicate that insulin and IGF-I, but not IGF-II, can induce rapid myofiber hypertrophy in vitro, most likely by stimulating myoblast proliferation and/or fusion to established myofibers.

Maintenance of highly contractile tissue-cultured avian skeletal myotubes in collagen gel

Abstract: Highly contractile skeletal myotubes differentiated in tissue culture are normally difficult to maintain on collagen-coated tissue culture dishes for extended periods because of their propensity to detach as a sheet of cells from their substratum. This detachment results in the release of mechanical tension in the growing cell “sheet” and, consequently, loss of cellular protein. We developed a simple method of culturing high density contractile primary avian myotubes embedded in a collagen gel matrix (collagel) attached to either a stainless steel mesh or nylon support structure. With this system the cells are maintained in a highly contractile state for extended periods in vitro under tension. Structural integrity of the myotubes can be maintained for up to 10 d in basal medium without serum or embryo extract. Total cellular protein and myosin heavy chain accumulation in the cells can be maintained for weeks at levels which are two to three times those found in timematched controls that are under little tension. Morphologically, the myotubes are well differentiated with structural characteristics of neonatal myofibers. This new collagel culture system should prove useful in the analysis of in vitro gene expression during myotube to myofiber differentiation and its regulation by various environmental factors such as medium growth factors, innervation, and mechanical activity.

Mechanotransduction across the cell surface and through the cytoskeleton

Abstract: Mechanical stresses were applied directly to cell surface receptors with a magnetic twisting device. The extracellular matrix receptor, integrin beta 1, induced focal adhesion formation and supported a force-dependent stiffening response, whereas nonadhesion receptors did not. The cytoskeletal stiffness (ratio of stress to strain) increased in direct proportion to the applied stress and required intact microtubules and intermediate filaments as well as microfilaments. Tensegrity models that incorporate mechanically interdependent struts and strings that reorient globally in response to a localized stress mimicked this response. These results suggest that integrins act as mechanoreceptors and transmit mechanical signals to the cytoskeleton. Mechanotransduction, in turn, may be mediated simultaneously at multiple locations inside the cell through force-induced rearrangements within a tensionally integrated cytoskeleton.

Cellular and Molecular Regulation of Muscle Regeneration

Abstract: Charge, Sophie B. P., and Michael A. Rudnicki. Cellular and Molecular Regulation of Muscle Regeneration. Physiol Rev 84: 209–238, 2004; 10.1152/physrev.00019.2003.—Under normal circumstances, mamma...

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

Abstract: Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Satellite Cells and the Muscle Stem Cell Niche

Abstract: Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process invol...