Myopathy in a rhesus monkey with biopsy findings similar to human sporadic inclusion body myositis.

A rhesus macaque with generalized muscle atrophy and musculotendinous contractures was detected in our research center. Muscle biopsies showed myofibers with rimmed vacuoles and eosinophilic hyaline inclusions, accumulations of CD8+ and CD4+ lymphocytes and expression of major histocompatibility complex class I in myofibers. Intracellular inclusions were positive to Congo red. Semithin sections and transmission electron microscopy showed autophagic vacuoles within myofibers and myonuclei with inclusions of filaments. These morphological observations conform with the diagnostic criteria of human sporadic inclusion body myositis. This is the first report of this myopathy in nonhuman primates.

Using the Montessori approach for a clientele with cognitive impairments: a quasi-experimental study design.

BACKGROUND: The choice of activities responding to the needs of people with moderate to severe dementia is a growing concern for care providers trying to target the need for a feeling of self-accomplishment by adapting activities to the abilities of elderly patients. The activities created by Maria Montessori seem to be adaptable to this clientele. This study evaluates the short-term effects, as compared to regular activities offered in the milieu. METHODS: This is a quasi-experimental study where each of the 14 participants was observed and filmed in two conditions: during Montessori activities, during regular activities, and one control condition (no activity). RESULTS: The results show that Montessori activities have a significant effect on affect and on participation in the activity. They support the hypothesis that when activities correspond to the needs and abilities of a person with dementia, these positive effects are also observed on behaviours. CONCLUSIONS: This study enabled its authors to corroborate the findings presented in the literature and to contribute additional elements on the positive effects of the use of Montessori activities and philosophy. Used with people with moderate to severe dementia these allow the satisfaction of their basic psychological needs, their well being, and hence, on their quality of life.

Intramuscular transplantation of human postnatal myoblasts generates functional donor-derived satellite cells.

Myogenic cell transplantation is an experimental approach for the treatment of myopathies. In this approach, transplanted cells need to fuse with pre-existing myofibers, form new myofibers, and generate new muscle precursor cells (MPCs). The last property was fully reported following myoblast transplantation in mice but remains poorly studied with human myoblasts. In this study, we provide evidence that the intramuscular transplantation of postnatal human myoblasts in immunodeficient mice generates donor-derived MPCs and specifically donor-derived satellite cells. In a first experiment, cells isolated from mouse muscles 1 month after the transplantation of human myoblasts proliferated in vitro as human myoblasts. These cells were retransplanted in mice and formed myofibers expressing human dystrophin. In a second experiment, we observed that inducing muscle regeneration 2 months following transplantation of human myoblasts led to myofiber regeneration by human-derived MPCs. In a third experiment, we detected by immunohistochemistry abundant human-derived satellite cells in mouse muscles 1 month after transplantation of postnatal human myoblasts. These human-derived satellite cells may correspond totally or partially to the human-derived MPCs evidenced in the first two experiments. Finally, we present evidence that donor-derived satellite cells may be produced in patients that received myoblast transplantation.

A first semimanual device for clinical intramuscular repetitive cell injections.

Intramuscular cell transplantation in humans requires so far meticulous repetitive cell injections. Performed percutaneously with syringes operated manually, the procedure is very time consuming and requires a lot of concentration to deliver the cells exactly in the required region. This becomes impractical and inaccurate for large volumes of muscle. In order to accelerate this task, to render it more precise, and to perform injections more reproducible in large volumes of muscle, we developed a specific semimanual device for intramuscular repetitive cell injections. Our prototype delivers very small quantities of cell suspension, homogeneously throughout several needles, from a container in the device. It was designed in order to deliver the cells as best as possible only in a given subcutaneous region (in our case, skeletal muscles accessible from the surface), avoiding wasting in skin and hypodermis. The device was tested in monkeys by performing intramuscular allotransplantations of beta-galactosidase-labeled myoblasts. During transplantations, it was more ergonomic and considerably faster than manually operated syringes, facilitating the cell graft in whole limb muscles. Biopsies of the myoblast-injected muscles 1 month later showed abundant beta-galactosidase-positive myofibers with homogeneous distribution through the biopsy sections. This is the first device specifically designed for the needs of intramuscular cell transplantation in a clinical context.

Ischemic central necrosis in pockets of transplanted myoblasts in nonhuman primates: implications for cell-transplantation strategies.

BACKGROUND: Several cell-transplantation strategies implicate the injection of cells into tissues. Avascular accumulations of implanted cells are then formed. Because the diffusion of oxygen and nutrients from the surrounding tissue throughout the implanted cell accumulations may be limited, central ischemic necrosis could develop. We analyzed this possibility after myoblast transplantation in nonhuman primates. METHODS: Macaca monkeys were injected intramuscularly with different amounts of myoblasts per single site. These sites were sampled 1 hr later and at posttransplantation days 1, 3, 5, and 7 and analyzed by histological techniques. RESULTS: One day posttransplantation, the largest pockets of implanted cells showed cores of massive necrosis. The width of the peripheral layer of living cells was approximately 100-200 microm. We thus analyzed the relationship between the amount of myoblasts injected per site and the volume of ischemic necrosis. Delivering 0.1 x 10(6) and 0.3 x 10(6) myoblasts did not produce ischemic necrosis; pockets of 1 x 10(6), 3 x 10(6), 10 x 10(6), and 20 x 10(6) myoblasts exhibited, respectively, a mean of 2%, 9%, 41%, and 59% of central necrosis. Intense macrophage infiltration took place in the muscle, invading the accumulations of necrotic cells and eliminating them by posttransplantation days 5 to 7. CONCLUSIONS: The desire to create more neoformed tissue by delivering more cells per injection site is confronted with the fact that the acute survival of the implanted cells is restricted to the peripheral layer that can profit of the diffusion of oxygen and nutriments from the surrounding recipient's tissue.

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.