Scientists grow leg muscle from cells in a dish

The scientists grew a leg muscle starting from engineered cells cultured in a dish to produce a graft. The subsequent graft was implanted close to a normal, contracting skeletal muscle where the new muscle was nurtured and grown. In time, the method could allow for patient-specific treatments for a large number of muscle disorders. The results are published in EMBO Molecular Medicine.

The scientists used muscle precursor cells – mesoangioblasts – grown in the presence of a hydrogel (support matrix) in a tissue culture dish. The cells were also genetically modified to produce a growth factor that stimulates blood vessel and nerve growth from the host.

Cells engineered in this way express a protein growth factor that attracts other essential cells that give rise to the blood vessels and nerves of the host, contributing to the survival and maturation of newly formed muscle fibres.

After the graft was implanted onto the surface of the skeletal muscle underneath the skin of the mouse, mature muscle fibres formed a complete and functional muscle within several weeks. Replacing a damaged muscle with the graft also resulted in a functional artificial muscle very similar to a normal Tibialis anterior.

Tissue engineering of skeletal muscle is a significant challenge but has considerable potential for the treatment of the various types of irreversible damage to muscle that occur in diseases like Duchenne muscular dystrophy.

So far, attempts to re-create a functional muscle either outside or directly inside the body have been unsuccessful. In vitro-generated artificial muscles normally do not survive the transfer in vivo because the host does not create the necessary nerves and blood vessels that would support the muscle's considerable requirements for oxygen.

“The morphology and the structural organisation of the artificial organ are extremely similar to if not indistinguishable from a natural skeletal muscle,” says Cesare Gargioli of the University of Rome, one of the lead authors of the study.

In future, irreversibly damaged muscles could be restored by implanting the patient's own cells within the hydrogel matrix on top of a residual muscle, adjacent to the damaged area. “While we are encouraged by the success of our work in growing a complete intact and functional mouse leg muscle we emphasize that a mouse muscle is very small and scaling up the process for patients may require significant additional work,” comments EMBO Member Giulio Cossu, one of the authors of the study. The next step in the work will be to use larger animal models to test the efficacy of this approach before starting clinical studies.

In vivo generation of a mature and functional artificial skeletal muscle

Claudia Fuoco, Roberto Rizzi, Antonella Biondo, Emanuela Longa, Anna Mascaro, Keren Shapira-Schweitzer, Olga Kossovar, Sara Benedetti, Maria L Salvatori, Sabrina Santoleri, Stefano Testa, Sergio Bernardini, Roberto Bottinelli, Claudia Bearzi, Stefano M Cannata, Dror Seliktar, Giulio Cossu and Cesare Gargioli.

Read the paper:

The paper will be available at 12.00 Central European Time at embomolmed.embopress.org. Please send an e-mail to barry.whyte@embo.org if you require a copy of the paper in the embargo period.

Further information on EMBO Molecular Medicine is available at embomolmed.embopress.org

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Barry Whyte
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EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work.

EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe. For more information: http://www.embo.org

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