Tissue Engineering Skeletal Muscle for Orthopaedic Applications

Payumo, Francis; Kim, Hyun D.; Sherling, Michael A.; Smith, Lee P.; Powell, Courtney; Wang, Xiao; Keeping, Hugh S.; Valentini, Robert F.; Vandenburgh, Herman H.

doi:10.1097/00003086-200210001-00027

Cited by 28 publications

(14 citation statements)

References 34 publications

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“…[1][2][3][4][5]9,[13][14][15][16] In traumatology, lost muscle is commonly observed to be eventually replaced by scar tissue. 6,17 Muscle loss is also encountered in pathological states, such as congenital abdominal wall defects (gastroschisis and omphalocele). A particular case of muscle loss is related to pedicled or microvascular muscle flaps in reconstructive plastic surgery.…”

Section: Discussionmentioning

confidence: 99%

Reconstruction of Ablated Rat Rectus Abdominis by Muscle Regeneration

Vindigni

Mazzoleni

Rossini

et al. 2004

Plastic and Reconstructive Surgery

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Skeletal muscle regeneration is a powerful, naturally occurring process of tissue reconstruction that follows myofiber damage secondary to myotoxic injury that does not normally affect the tissue circulation and scaffold. The ablated tissue, in traumatology and free muscle grafts, is frequently replaced by scars. The final outcome is poor even after in situ myoblast seeding of the harvested muscle. The goal of this study was to identify protocols to reconstruct muscle tissue, even in such adverse environments. The authors applied a step-by-step approach to identify factors favoring the survival of autologous satellite cells and, thus, muscle regeneration. In a rat model of full-thickness rectus abdominis muscle ablation, autologous myoblasts were isolated from the explanted rectus abdominis and seeded in a homologous acellular matrix immediately after wall reconstruction (group 1, five animals). In group 2 (five animals), the ablated rectus abdominis was autografted in situ. In a third group of five rats, Marcaine was injected into both the autograft and the surrounding abdominal wall muscle. Three weeks after surgery, serial cross-sections of the reconstructed abdominal wall were stained with hematoxylin and eosin or embryonic myosin antibody, a well-characterized molecular marker of early myogenesis in development and regeneration. Percentages of the patch area covered by regenerated myofibers were determined by morphometry. When autologous myoblasts were seeded in a homologous acellular matrix, the only myofibers observed to regenerate were those along the border of the patch. Autografting of the middle third of the rectus abdominis muscle similarly resulted in scar formation. The few muscle cells in the graft core were scanty myoblasts that could be detected only by monoclonal embryonic myosin antibody. Although negative for myofiber regeneration, the results in both cases confirmed the mechanical patency of the patches with regard to abdominal organ support. Myofibers were successfully regenerated in the graft by injecting Marcaine into both the autograft and the surrounding muscles. Three weeks after surgery, the patch was paved with young, centrally nucleated myofibers intermixed with young myofibers and myotubes expressing embryonic myosin. The difference in percentage of patch area covered by regenerated myofibers in group 3 (Marcaine injection around the patch, 81.6 +/- 3.0 percent) (mean +/- SD) versus either group 1 (Myoblast-seeded acellular patch, 18.0 +/- 3.0 percent) or group 2 (Autograft, 25.8 +/- 7.0 percent) was statistically significant on independent t test analysis (p < 0.0001). Even an acellular matrix showed some myofiber regeneration after surrounding muscles had been injected with Marcaine. This is the first successful evidence of muscle reconstruction after full-thickness ablation of the middle third of the rectus abdominis. Muscle regeneration seems to be the result of successive waves of migration of angioblasts and then satellite cell-derived myoblasts from the muscles surrounding th...

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Section: Discussionmentioning

confidence: 99%

Reconstruction of Ablated Rat Rectus Abdominis by Muscle Regeneration

Vindigni

Mazzoleni

Rossini

et al. 2004

Plastic and Reconstructive Surgery

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“…Human myoblasts were successfully transduced ex vivo with a retroviral vector to secrete 0.5 -2 µg rhGH/million cells/day, and were tissue-engineered into human BAM containing parallel arrays of differentiated post-mitotic myofibres [124] . Similar technology was used to develop a vehicle for paracrine release of IGF-I [125] or systemic bone morphogenetic protein delivery in vivo , where proliferating skeletal myoblasts (C2C12) were transduced with a replicationdefective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6) [126] . Other groups used a similar approach, using primary human muscle-derived cells as an ex vivo gene therapy to deliver BMP2 and to produce bone in vivo [127] .…”

Section: Growth Hormone-relatedmentioning

confidence: 99%

Update on emerging drugs for sarcopenia – age-related muscle wasting

Lynch

2008

Expert Opinion on Emerging Drugs

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Sarcopenia -the progressive loss of muscle mass with advancing age is characterised by a deterioration of muscle quantity and quality leading to a gradual slowing of movement and a decline in strength and power. Sarcopenia is a highly significant public health problem. Frail elders often require assistance for accomplishing even basic tasks of independent living, and they are also at increased risk of serious injury from sudden falls and subsequent fractures. Since these age-related changes are largely attributed to the complex interaction of factors affecting neuromuscular transmission, muscle architecture, fibre composition, excitation-contraction coupling, and metabolism, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for novel drug discovery. Objective : This review provides an update on some of the emerging drugs for sarcopenia that have been in development during 2005 -2008. Methods : This is a review of the current status of emerging therapies and novel approaches for sarcopenia. Results : Considerable research and development in academic and research institutions and in large and small pharma is being directed to sarcopenia and related health issues; specifically the development and evaluation of novel therapeutic strategies to attenuate, prevent, or ultimately reverse age-related muscle wasting and weakness. Conclusions : Few, if any, drugs have been developed for sarcopenia specifically, but there are many existing and emerging drugs that have potential application for tackling age-related muscle wasting, particularly drugs for neurodegenerative diseases.

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“…Apart from its clinical relevance to myopathies and limb regeneration, primary muscle culture has recently received enormous attention from multi-disciplinary fields such as tissue engineering, cell-patterning and robotics [9][10][11][12]. Differentiation of skeletal muscle is a highly controlled multi-step process, during which single muscle cells initially freely divide and then align and fuse to form multinucleated myotubes.…”

Section: Introductionmentioning

confidence: 99%