Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients.
Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of a functional dystrophin in muscles results in the fragility of the muscle fiber membrane with progressive muscle weakness and premature death. There is no cure for DMD and current treatment options focus primarily on respiratory assistance, comfort care, and delaying the loss of ambulation. Recent works support the idea that stem cells can contribute to muscle repair as well as to replenishment of the satellite cell pool. Here we tested the safety of autologous transplantation of muscle-derived CD133+ cells in eight boys with Duchenne muscular dystrophy in a 7-month, double-blind phase I clinical trial. Stem cell safety was tested by measuring muscle strength and evaluating muscle structures with MRI and histological analysis. Timed cardiac and pulmonary function tests were secondary outcome measures. No local or systemic side effects were observed in all treated DMD patients. Treated patients had an increased ratio of capillary per muscle fibers with a switch from slow to fast myosin-positive myofibers.
Torrente
Y
Y
Fondazione IRCCS Ospedale Maggiore Policlinico of Milan, Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Italy. torrenteyvan@hotmail.com
Belicchi
M
M
Marchesi
C
C
D'Antona
G
G
Cogiamanian
F
F
Pisati
F
F
Gavina
M
M
Giordano
R
R
Tonlorenzi
R
R
Fagiolari
G
G
Lamperti
C
C
Porretti
L
L
Lopa
R
R
Sampaolesi
M
M
Vicentini
L
L
Grimoldi
N
N
Tiberio
F
F
Songa
V
V
Baratta
P
P
Prelle
A
A
Forzenigo
L
L
Guglieri
M
M
Pansarasa
O
O
Rinaldi
C
C
Mouly
V
V
Butler-Browne
G S
GS
Comi
G P
GP
Biondetti
P
P
Moggio
M
M
Gaini
S M
SM
Stocchetti
N
N
Priori
A
A
D'Angelo
M G
MG
Turconi
A
A
Bottinelli
R
R
Cossu
G
G
Rebulla
P
P
Bresolin
N
N
D000071916:AC133 Antigen; D000293:Adolescent; D015703:Antigens, CD / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D002648:Child; D004311:Double-Blind Method; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D018189:Immunomagnetic Separation / Q000145:classification; D016130:Immunophenotyping / Q000145:classification; D007273:Injections, Intramuscular; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology / Q000628:therapy*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000637:transplantation*; D010455:Peptides / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides