Cellular therapy has evolved since the first blood transfusion. Using specialized techniques, it has been possible to recognize and isolate the cells responsible of the repair of particular tissues like muscles. It is actually possible to isolate these “'satellite cells” from a healthy donor and then to culture them in laboratory. Placing only one “'satellite cells” in adequate specific medium and providing it the necessary nutrients, we can obtain more than ten millions after one month of culture! These cells can be transplanted to repair damaged muscles.
Each one of our cells contains DNA which, can be compared to an enormous book containing nearly 30.000 different instructions. Each instruction, more commonly called “genes”, permits the cell to produce a “protein”. If the instruction is not read correctly, there can be development of a disease. How a genetic defect can occur? When a cell divides to give rise to two cells, it must make a copy of its ADN. Unfortunately, it happens that an error occurs and that an instruction becomes unreadable. For the DMD patients, muscles are deprived from a protein called “dystrophin”. This protein is responsible of the resistance of our muscles. The incapacity to produce dystrophine is so responsible for the deterioration of the muscles within DMD pateints. The damaged muscle fibres are repaired by the proliferation of small cells, called satellite cells which, are located close to each muscle fibre. Unfortunately the repaired muscle fibers are always deprived of dystrophin and will be damaged again. The repeated cycles of degeneration and regeneration lead to the senescence of the myoblasts and thus to a decreased capacity of regeneration leading to the weakness of the muscles(Fig. 1).
A muscle, like the biceps, is composed of thousands of muscle fibers. To give rise to a muscle fiber, several hundreds of cells must align and fuse (Fig. 2). Following damage, repairing cells present in our muscles are activated and fuse with our fibers to repair them. In DMD child, the lack of dystrophin makes muscle fibres more fragile than those of a normal person. The disease was described by Dr Guillaume Duchenne de Boulogne 135 years ago and no treatment exist to date to cure this pathology. The research carried out in our laboratory is to develop a therapy which, consists in isolating satellite cells from healthy person and to transplant them into DMD muscle. Cellular transplantation consists in injecting into the DMD patient muscle, healthy cells containing the instructions necessary to produce the dystrophin. The injection of these new cells permits to reconstitute a reserve of repairing cells able to fuse with fibres of the patient (Fig. 3).
Once fused with the “sick” fibre, the healthy cell will be able to produce the missing protein, the dystrophin.
The results which, we obtained within DMD patients are very encouraging (Fig. 4). This therapy reached today the clinical phase I and constitutes the most advanced treatment for the DMD. By injecting the cells directly in the muscles of the patient, we hope to give him the force, move the arms and to use his hands. Although it remains much improvements to bring in order to be able to treat this disease, the hope to cure the dystrophic patients completely is quite concrete and is limited only by the advances in the research and in our knowledge.