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Biomedical subjects

J Huard

Publications and source records attributed to J Huard.

98 records · Page 6Linked to original sources
PubMedDate not supplied

The use of an antifibrosis agent to improve muscle recovery after laceration.

Muscle injuries are challenging problems in traumatology and the most frequent injuries in sports medicine. Muscle injuries are capable of healing, although slowly and occasionally with incomplete functional recovery. We observed that lacerated muscle undergoes a rapid process of regeneration, which is hindered by the development of fibrosis. Biologic approaches to enhance muscle regeneration and prevent fibrosis are being investigated to improve muscle healing after injuries. We observed that growth factors can improve muscle regeneration but cannot prevent muscle fibrosis. We investigated the use of an antifibrosis substance, decorin, as an approach to prevent fibrosis and thereby improve muscle healing after injury in murine muscle. We observed that direct injection of human recombinant decorin can efficiently prevent fibrosis and enhance muscle regeneration in the lacerated muscle. More importantly, decorin can improve the recovery of strength in the injured muscle to a level similar to that observed in normal noninjured muscle. These results suggest that injection of decorin improves both the muscle structure and the function of the lacerated muscle to near complete recovery. This study will contribute significantly to the development of strategies to promote efficient muscle healing and complete functional recovery after muscle injuries.

Animals↗
PubMedDate not supplied

Suturing versus immobilization of a muscle laceration. A morphological and functional study in a mouse model.

Muscle laceration remains a difficult problem for orthopaedic surgeons. Despite many studies related to the muscle's ability to regenerate after muscle degeneration, very few reports are available regarding structural and functional recovery after skeletal muscle laceration. We developed an animal model of muscle laceration in mice, where the gastrocnemius muscles were reproducibly transected. We compared the effect of a surgical repair versus a short period of immobilization (5 days) on the muscle healing. The natural course of muscle recovery was monitored at several points after injury using histologic, immunohistochemical, and functional testing. In the injured muscle, we observed a high number of regenerating myofibers and development of fibrotic scar tissue. Suturing the lacerated muscle immediately after injury promoted better healing of the injured muscle and prevented the development of deep scar tissue in the lacerated muscle; conversely, immobilization resulted in slower muscle regeneration and the development of a large area of scar tissue. Tetanus strength 1 month after injury was 81% of control muscles for the sutured muscles, 35% for the lacerated muscles with no treatment, and 18% for the immobilized muscles. Based on this study, suturing a muscle laceration with a modified Kessler stitch results in the best morphologic and functional healing.

Analysis of Variance↗
PubMedDate not supplied

The efficiency of muscle-derived cell-mediated bone formation.

The development of new clinically applicable methods for the delivery of bone morphogenic protein (BMP) is an area of intensive research. Cell-mediated gene therapy approaches are being explored as a potential delivery vehicle. Primary muscle-derived cells isolated from an adult mouse were transduced with an adenoviral-BMP-2 construct. These cells were injected into the triceps surae of severe combined immune deficient (SCID) mice where they induced heterotopic bone formation. BMP-2 expression by these muscle-derived cell constructs was measured in vitro to estimate in vivo BMP-2 delivery. In vitro expression of BMP-2 by 3 x l0(5) muscle-derived cells was 87.89 ng/72 h. These results suggest that the efficiency of muscle cell-based gene delivery of BMP-2 exceeds the direct delivery of recombinant BMP-2 protein.

Animals↗
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The influence of muscle fiber type in myoblast-mediated gene transfer to skeletal muscles.

Myoblast transplantation has been hindered by immune rejection problems, as well as the poor survival and spread of transplanted cells. Our recent study has shown that the poor survival of the injected cells can be totally overcome by the use of specific populations of muscle-derived cells. In the present study, we have investigated whether a relationship exists between the fate of transplanted cells and the muscle fiber types. Four kinds of myogenic cells [primary myoblasts at a high purity (PMb), myoblasts isolated from fast single fibers (FMb), mdx (MCL), and MtMd-1 cell lines] were infected with an adenoviral vector carrying a LacZ reporter gene and injected into mdx hindlimb muscle. The LacZ transduced myofibers formed by the fusion of the injected myoblasts at 2-10 days postinjection were colocalized with MyHC stainings. The PMb cells, which expressed both slow and fast MyHCs in vitro, displayed the same phenotypes when injected into the m. soleus and m. gastrocnemius (white) muscles, which contained 70% and 0% of slow myofibers, respectively, and showed a high degree of fusion with host muscle fibers. In contrast, the FMb cells only expressed fast MyHCs in vitro and fused exclusively with each other or with host fast muscle fibers when injected in the m. gastrocnemius. Injected MCL and MtMd-1 fused predominantly with each other and displayed a similar expression of MyHCs to those they expressed in vitro. Just a few host myofibers were found to express the reporter gene product following implantation of both cell lines, indicating that these myogenic cell lines display an intrinsic potential to fuse together rather than with host myofibers. Based on the data, we concluded that 1) the essential key to survival is the ability of the donor cells to fuse with the host myofibers, and 2) the most successful combination is achieved between donor primary muscle cells that express both fast and slow MyHC and a host muscle type that facilitates fusion.

Animals↗
PubMedDate not supplied

Results of a triple blind clinical study of myoblast transplantations without immunosuppressive treatment in young boys with Duchenne muscular dystrophy.

The effects of myoblast transplantations without an immunosuppressive treatment on muscle strength, and the formation of dystrophin-positive fibers was studied in five young boys with Duchenne muscular dystrophy (DMD) using a triple blind design. Injections of myoblasts were made into one biceps brachii (BB), and the opposite BB, used as a control, was sham-injected; the experimenters and the patient were blind to the myoblast-injected side. At the same time, myoblasts were also injected in the left tibialis anterior (TA) of these patients. The strength developed during maximal static contractions of the elbow flexor and extensor muscles was measured with a Kin-Com dynamometer. No increase in static elbow flexion torque was measured at any time from 2 mo up to 18 mo after the transplantation. One month after the transplantation, the percentage of dystrophin-positive fibers in the myoblast-injected TA ranged from 0 to 36%, while it ranged from 0 to 4% on the control side. The expression of dystrophin in these fibers, however, was generally low, and most likely less than 10% of the normal level. In the biceps brachii of both sides 6 mo after the transplantation, less than 1.5% of dystrophin-positive fibers were detected. The injections also triggered a humoral immune response of the host. Antibodies were capable of fixing the complement, and of lysing the newly formed myotubes. One of the antigens recognized by this immune response is possibly dystrophin. These results strongly suggest that myoblast transplantations, as well as gene therapy for DMD, cannot be done without immunosuppression.

Biopsy↗
PubMedDate not supplied

Utilization of an antibody specific for human dystrophin to follow myoblast transplantation in nude mice.

Human myoblasts were transplanted in nude mice. The efficacy of these transplantations was analyzed using a monoclonal antibody (NCLDys3) specific for human dystrophin. This antibody did not reveal any dystrophin in nude mice that did not receive a human myoblast transplantation. However, about 30 days after a human myoblast transplantation, dystrophin-positive muscle fibers were observed. They were not abundant, and were present either in small clusters or isolated. This technique follows the fate of myoblast transplantation in animals that already have dystrophin, and distinguishes between new dystrophin-positive fibers due to the transplantation and the revertant fibers in mdx mice. Moreover, this technique does not require any labelling of the myoblasts before transplantation. It can also be used to detect dystrophin produced following the fusion of myoblasts transfected with the human dystrophin gene.

Adolescent↗
PubMedDate not supplied

Development of approaches to improve the healing following muscle contusion.

Muscle injuries are a challenging problem in traumatology, and the most frequent occurrence in sports medicine. Muscle contusions are among the most common muscle injuries. Although this injury is capable of healing, an incomplete functional recovery often occurs, depending on the severity of the blunt trauma. We have developed an animal model of muscle contusion in mice (high energy blunt trauma) and characterized the muscle's ability to heal following this injury using histology and immunohistochemistry to determine the level of muscle regeneration and the development of scar tissue. We have observed a massive muscle regeneration occurring in the first 2 wk postinjury that is subsequently followed by the development of muscle fibrosis. Based on these observations, we propose that the enhancement of muscle growth and regeneration, as well as the prevention of fibrotic development, could be used as approach(es) to improve the healing of muscle injuries. In fact, we have identified three growth factors (bFGF, IGF-1, and NGF) capable of enhancing myoblast proliferation and differentiation in vitro and improving the healing of the injured muscle in vivo. Furthermore, the ability of adenovirus to mediate direct and ex vivo gene transfer of beta-galactosidase into the injured site opens possibilities of delivering an efficient and persistent expression of these growth factors in the injured muscle. These studies should help in the development of strategies to promote efficient muscle healing with complete functional recovery following muscle contusion.

Animals↗