Improvement of contraction force in injured skeletal muscle after autologous mesenchymal stroma cell transplantation is accompanied by slow to fast fiber type shift.
BACKGROUND
Skeletal muscle trauma leads to severe functional deficits, which cannot be addressed by current treatment options. Previous investigation could show the efficacy of a local transplantation (TX) of mesenchymal stroma cells (MSCs) for the therapy of muscle injury. Underlying mechanisms remain to be elucidated. The aim of the present work was to characterize the fiber composition changes following MSC-TX after open crush injury.


METHODS
20 male SD rats received an open crush trauma of the left soleus muscle. 2.5 × 10(6) autologous MSCs were transplanted into the crushed soleus muscle of 10 animals 7 days after trauma (group 1, n = 10). Control animals received an injection of saline solution (group 2, n = 10). Histologic analysis of fibrosis, fiber type composition, and muscle force measurements were performed 28 days after trauma.


RESULTS
MSC-TX improved muscle force significantly (fast-twitch, treated: 0.76 (0.51-1.15), untreated: 0.45 (0.32-0.73); p = 0.01). Tetanic stimulation resulted in a significant increase of force development (treated: 0.63 (0.4-1.21), untreated: 0.34 (0.16-0.48); p = 0.04). Histological analyses showed no differences in the amount of fibrotic tissue (treated vs. untreated, p = 0.42). A shift towards fastMHC-positive fibers was observed following MSC-TX (treated vs. untreated; p = 0.01 (mm(2)) or 0.007 (%)).


CONCLUSIONS
This study demonstrated an effect of locally administered MSCs in the treatment of skeletal muscle injuries on a structural level. For the first time a fiber type shift towards fastMHC following MSC-TX after crush injury could be demonstrated and related to MSC-TX. These results might open the discussion of an alternative mode of action of MSCs in tissue regeneration.
Center for Musculoskeletal Surgery, Julius Wolff Institute, Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Germany.
Philipp
P
von Roth
Center for Musculoskeletal Surgery, Julius Wolff Institute, Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Germany.
Tobias
T
Winkler
Center for Musculoskeletal Surgery, Julius Wolff Institute, Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Germany.
Kristina
K
Rechenbach
Center for Musculoskeletal Surgery, Julius Wolff Institute, Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Germany.
Piotr
P
Radojewski
Center for Musculoskeletal Surgery, Julius Wolff Institute, Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Germany.
Carsten
C
Perka
Center for Musculoskeletal Surgery, Julius Wolff Institute, Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Germany.
Georg N
GN
Duda
Fast myosin heavy chain; Fiber type; Muscle trauma; Regeneration; Shift; Slow myosin heavy chain; Stem cells; Tissue engineering