Evidence of fusion between host and donor myoblasts in skeletal muscle grafts.
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Animals↗
Biomedical subjects
T A Partridge
Publications and source records attributed to T A Partridge.
A host contribution to the regeneration of muscle grafts.
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Animals↗
Macrophage migration inhibition studies of lymphocytes taken from guinea-pigs suffering from experimental polymyositis.
An experimental form of polymyositis, induced in guinea-pigs by means of injections of rabbit muscle homogenate in Freund's complete adjuvant (FCA), had been investigated with a view to the analysis of the role of cellular immune response in this disease. We have used the direct macrophage migration inhibition test on peritoneal exudate cells taken from myositic animals, so as to identify those components of muscle against which lymphocytes of myositic animals are sensitized. These lymphocytes were found to be sensitized principally against the myofibrillar fraction of muscle. Moreover, when tested against purified myofibrillar proteins, they were found to be strongly sensitized against myosin and tropomyosin, but not against troponin. A similar migration inhibition technique is now being developed for use as a diagnostic and investigatory tool in the study of human polymyositis.
Animals↗
A quantitative test to detect lymphocytes sensitized against the surface of muscle cells.
A test is described which assesses quantitatively the capacity of lymphocytes taken from myositic animals to adhere to skeletal muscle cells in vitro. Lymphocytes were taken from guinea-pigs in which a polymyositis had been induced by injection of rabbit skeletal muscle and complete Freund's adjuvant. These lymphocytes attached themselves preferentially to multinucleate myotubes as opposed to the mononuclear cells in tissue cultures made from chick skeletal muscle. The degree of preference was calculated as a Preferential Attachment (PA) index. This index was high in those animals which developed myositis. In contrast lymphocytes from various groups of control guinea-pigs all gave a PA index of around 1. This test is now being adapted for use in the diagnosis and study of polymyositis in human patients.
Animals↗
The role of myofibrillar fraction of skeletal muscle in the production of experimental polymyositis.
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Animals↗
Use of mononuclear precursor cells to insert allogeneic genes into growing mouse muscles.
Our long-term aim is to use allografts of normal muscle precursor cells to insert donor myonuclei, containing a normal genome, into the growing defective muscle fibers of young animals with inherited myopathies. In the present article, we have used isoenzyme variants of glucose-6-phosphate isomerase (GPI) as genetic markers of host and donor genomes in the mouse. We show that mononucleated cells, prepared by enzymatic disaggregation of neonatal donor muscle, 39 can be used to introduce donor GPI genes into muscle fibers of growing muscles of young hosts. The expression of both donor and host GPI genes in the resulting mosaic muscle fibers leads to the formation of a "hybrid" GPI isoenzyme dimer. Such hybrid GPI was found in 10 of 102 host muscles examined. Our results indicate that grafts of muscle precursor cells can be used to alter the genetic constitution of both normal and mildly myopathic muscle.
Animals↗
The mdx mouse skeletal muscle myopathy: I. A histological, morphometric and biochemical investigation.
Skeletal muscle has been examined in a colony of the mdx strain of myopathic mice. Sixty-five mice from 22 to 303 days of age, showed extensive and recurrent areas of necrosis and regeneration of muscle fibres, often accompanied by active cellular infiltration. Morphometry of the soleus muscle revealed an abnormal proportion of small and large muscle fibres; over half of the muscle fibres contained 'central' (non-peripheral) nuclei. No histochemical muscle fibre-type grouping was detected. Serum activities of muscle-derived enzymes were greatly elevated in all animals and probably reflect enzyme leakage from damaged muscle fibres. Histological evidence of a cardiomyopathy was found in 13 mice. The mdx myopathy thus shows features seen in Duchenne muscular dystrophy. Mdx differs from Duchenne dystrophy principally in that it exhibits a greater degree of compensatory muscle regeneration and an absence of fibro-fatty replacement of muscle fibres.
Adenosine Triphosphatases↗
The mdx mouse skeletal muscle myopathy: II. Contractile properties.
The contractile properties of soleus muscles from mdx and control mice aged between 26 and 350 days were compared with those of muscles from similarly aged control mice. Mdx mice were in general heavier (their individual soleus muscles were also heavier), of greater cross-sectional area and greater standard length than age-matched controls. Isometric forces produced by soleus muscles from young mdx mice (less than or equal to 100 days) were similar to controls, but were weaker when force was normalized for cross-sectional area. Conversely, although the absolute isometric forces produced by older (greater than 100 days) mdx muscles were greater than age-matched controls, when normalized for cross-sectional area they were similar. No differences were found between mdx and control muscles in terms of length-force or force-velocity relationships. Thus, young mdx control muscles produce similar absolute isometric force but mdx mouse muscles are larger. When muscle size is accounted for, in terms of cross-sectional area, younger mdx muscles are, therefore, weaker than controls. Inefficient contraction of young mdx muscles may result from lack of contractile fibres, physiological inefficiency of contractile fibres, or loss of tendon-fibre continuity during muscle fibre necrosis and regeneration. The striking supernormal size and strength of older mdx muscles reflects their considerable regenerative capacity; whether this is due to an increase in muscle fibre number rather than fibre hypertrophy remains unclear.
Aging↗
Thymic myoid cells as a source of cells for myoblast transfer.
Transplantation of disaggregated myoblasts from normal donor to the muscles of a diseased host, or reimplantation of genetically modified host myoblasts, has been suggested as a possible route to therapy for inherited myopathies such as Duchenne muscular dystrophy, or to supply missing proteins that are required systemically in diseases such as hemophilia. With two exceptions, studies of myoblast transfer in the mouse have involved transplantation of donor myoblasts isolated from adult or neonatal skeletal muscle satellite cells. In this study we present evidence that thymic myoid cells are capable of participating in the regeneration of postnatal skeletal muscle, resulting in the expression of donor-derived proteins such as dystrophin and retrovirally encoded proteins such as beta-galactosidase within host muscles. This leads us to conclude that thymic myoid cells may provide an alternative to myoblasts derived from skeletal muscle as a source of myogenic cells for myoblast transfer.
Animals↗