Myogenic Expression of Mesenchymal Stem Cells within Myotubes of mdx Mice in Vitro and in Vivo.
The myogenic potential of bone marrow- and periosteum-derived mesenchymal stem cells (MSCs) was studied in vitro by coculture of MSCs of snj mice with myoblasts of newborn snj mice or 3-week-old mdx mice. MSCs were labeled with [(3)H]thymidine and cocultured with muscle precursor cells. At 5 different time points, the cocultures were harvested and prepared for autoradiography. Cocultures of MSCs and mdx mouse-derived myoblasts were immunostained for dystrophin before autoradiography. Autoradiographic grains were detected over isolated nuclei in myotubes, which stained positively with antidystrophin antibody. In vivo myogenic potential of MSCs was tested by direct injection into growing muscle of mdx mice. Equal numbers of nonmutant bone marrow-derived MSCs or myoblasts were injected separately into the tibialis anterior muscles of mdx mice. Muscle samples were harvested at 6, 8, and 10 weeks after injection, weighed, and stained with antidystrophin antibody. A small yet significant increase in muscle mass was observed in both the myoblast-injected (11% increase) and MSC-injected muscles (3%), as compared to controls. Muscle injected with myoblasts showed a remarkable conversion from dystrophin-negative to dystrophin-positive fibers (30-40%) in mdx mice injected with normal myoblasts, as previously reported by others. The frequency of dystrophin-positive fibers in mdx mouse muscle injected with marrow-derived MSCs was lower than that of the muscles injected with myoblasts, but was significantly higher than control muscles injected with medium. These results suggest that within the population of MSCs there are cells that are able to differentiate into skeletal muscle.
Saito
T
T
Department of Orthopaedic Surgery, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan.
Dennis
J E
JE
Lennon
D P
DP
Young
R G
RG
Caplan
A I
AI