First test of a "high-density injection" protocol for myogenic cell transplantation throughout large volumes of muscles in a Duchenne muscular dystrophy patient: eighteen months follow-up.
A 26-years old Duchenne muscular dystrophy (DMD) patient received normal muscle-precursor cells, proliferated in vitro and implanted in a thenar eminence, biceps brachii, and in a portion of a gastrocnemius by injections placed 1mm from each other or less. Saline was injected in the contralateral gastrocnemius. The patient was immunosuppressed with tacrolimus. The protocol of cell transplantation was well tolerated and did not cause permanent sequels. Some injected sites were biopsied at 1, 14 and 18 months post-transplantation. Muscles were replaced by fat and fibrosis. In the cell-grafted site of the gastrocnemius, 27.5% of the myofiber profiles expressed donor-derived dystrophin 1 month post-transplantation and 34.5% 18 months post-transplantation. The contralateral gastrocnemius was dystrophin-negative. Myofibers were virtually absent in the biceps brachii, where only two dystrophin-positive myofibers were observed. In conclusion, a "high-density injection" protocol was feasible for intramuscular cell-transplantation in a DMD patient and long-term expression of donor-derived dystrophin was observed.
Skuk
Daniel
D
Unité de Recherche en Génétique Humaine, Centre Hospitalier de l'Université Laval, Laurier, QUE, Canada.
Goulet
Marlyne
M
Roy
Brigitte
B
Piette
Vincent
V
Côté
Claude H
CH
Chapdelaine
Pierre
P
Hogrel
Jean-Yves
JY
Paradis
Martin
M
Bouchard
Jean-Pierre
JP
Sylvain
Michel
M
Lachance
Jean-Guy
JG
Tremblay
Jacques P
JP
D000704:Analysis of Variance; D017690:Cell Transplantation / Q000379:methods*; D016189:Dystrophin / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D032342:Muscle Cells / Q000276:immunology / Q000637:transplantation*; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery*; D013997:Time Factors
D016189:Dystrophin; D007166:Immunosuppressive Agents