EMBO: A team of researchers from Italy, Israel and the United Kingdom has
succeeded in generating mature, functional skeletal muscles in mice
using a new approach for tissue engineering. 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:
doi: 10.15252/emmm.201404062