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Allied Journal of Medical Research
|
Volume 2
Page 45
allied
academies
CANCER THERAPY AND ONCOLOGY
NEUROLOGY AND BRAIN DISORDERS
&
International Conference on
International Conference on
J u n e 2 1 - 2 2 , 2 0 1 8 | O s a k a , J a p a n
Joint Event on
CLINICAL TRIALS OF CELL THERAPIES IN NEUROMUSCULAR
DISEASES
Daniel Skuk
Research Center of the CHU de Quebec, Canada
C
ell therapy is an experimental strategy for a potential treatment of genetic and / or degenerative muscular disorders, among which
the most important target is Duchenne muscular dystrophy (DMD). To be used in this approach, the cells must be myogenic, that
is, they must have at least one of the following properties: (1) fuse with the patient’s myofibers to induce the expression of therapeutic
proteins in them, (2) form new myofibers, and / or (3) give rise to new muscle specific stem cells (satellite cells). Considering reports of
experiments conducted on mice and dogs, the repertoire of cells exhibiting some of the myogenic capacities seems to have expanded
in recent years. Among these cells we have: CD56+ muscle-derived cells, muscle-derived stem cells, CD133+ cells, mesoangioblasts /
pericytes, myoendothelial cells, ALDH+ cells, PW1+/Pax7– interstitial cells, and ß-4-integrin+ cells. The clinical studies of cell therapy
conducted so far showed that, of the four cell types transplanted in patients with DMD, namely CD56+ muscle-derived cells, bone marrow
derived cells, CD133+ cells and mesoangioblasts, the only for which there were observed myogenic properties in the clinics were CD56+
muscle-derived cells, that is, satellite cell derived myoblasts. In a clinical trial, we allotransplanted CD56+ muscle-derived cells in 1 cm3 of
muscle in 9 patients with DMD immunosuppressed with tacrolimus. Four weeks later, we observed restoration of the therapeutic protein
(dystrophin) in 3.5% to 26% myo bers. Evidences of small myo ber neoformation and of potentially graft-derived satellite cells were also
observed. A 26-years old DMD patient also received cell allotransplantations under tacrolimus immunosuppression in different muscles,
restoring dytrophin in 27.5% of myo bers at 1 month and in 34.5% at 18 months. This patient evidenced that our protocol was feasible in
large muscles of humans and that long-term expression of donor-derived dystrophin can be obtained under proper immunosuppression.
Further improvements are desirable for efficient clinical applications of this strategy and we are currently working on it.
Daniel.Skuk@crchudequebec.ulaval.caAllied J Med Res 2018, Volume 2