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Homologous muscle acellular matrix seeded with autologous myoblasts as a tissue-engineering approach to abdominal wall-defect repair

Section of Anatomy, Department of Human Anatomy and Physiology, University of Padova, Via Gabelli 65, I-35121 Padova, Italy.
Biomaterials (Impact Factor: 8.31). 06/2005; 26(15):2567-74. DOI: 10.1016/j.biomaterials.2004.07.035
Source: PubMed

ABSTRACT Myoblasts were obtained by culturing in vitro, single muscle fibers, isolated by enzymatic digestion from rat flexor digitorum brevis, and their phenotype was confirmed by myogenic differentiation factor, myogenic factor-5, myogenin and desmin. Cultured myoblasts were harvested and seeded on patches of homologous acellular matrix, obtained by detergent-enzymatic treatment of abdominal muscle fragments. Myoblast-seeded patches were inserted between obliqui abdominis muscles on the right side of 1-month-old rats, while non-seeded patches were implanted on the left side. Thirty days after surgery, non-seeded patches were completely replaced by fibrous tissue, while the structure of myoblast-seeded patches was well preserved until the 2nd month. Seeded patches displayed abundant blood vessels and myoblasts, and electromyography evidenced in them single motor-unit potentials, sometimes grouped into arithmic discharges. Ninty days after implantation, the thickness of myoblast-seeded patches and their electric activity decreased, suggesting a loss of contractile muscle fibers. In conclusion, the present results indicate that autologous myoblast-homologous acellular muscle matrix constructs are a promising tool for body-wall defect repair, and studies are under way to identify strategies able to improve and maintain the structural and functional integrity of implants for longer periods.

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    • "Whether MAS is a good support for cells of non-muscle origin and whether it can be exploited in trans-species experiments , such as cultivating human cells in murine MAS, remains to be addressed. However, accumulating evidence suggests that acellular scaffolds of biological origin are multipurpose and may be exploited for cell culture and tissue engineering of different tissue types regardless of their origin (Badylak et al., 1998; Conconi et al., 2005; Wolf et al., 2012). It is widely accepted that the niche supports stem cells and controls their self-renewal in vivo (Spradling et al., 2001) by modulating asymmetric cell division and ensuring stem cell renewal and the production of a number of committed daughter cells that is sufficient for tissue homeostasis and repair (Kuang et al., 2008). "
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    • "The resulting scaffold supported myoblast growth and differentiation in vitro. When the decellularized muscle seeded with myoblasts was implanted between the obliquus externus abdominis and the obliquus internus abdominis, neovascularization and the formation of new myofibers occurred within 2 months (Conconi et al., 2005). Merritt et al. decellularized a rat gastrocnemius (GAS) by means of a protocol based on osmotic shock and detergent solutions that required several days (Merritt et al., 2010b). "
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    • "In line with our findings, an increase in HA and TN within the interstitial matrix induced by myofiber damage may enhance myoblast proliferation and migration while inhibiting premature fusion, allowing for more extensive repair of the musculature. Nevertheless, attempts to engineer replacements for skeletal muscle defects tend to rely upon exogenous scaffolding composed of either inert polymers or ECM typical of the differentiated state, which promotes fusion, reduces cell proliferation and ultimately results in limited functionality (Conconi et al., 2005; Kin et al., 2007; Merritt et al., 2010). "
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