Implanted myoblasts not only fuse with myofibers but also survive as muscle precursor cells

1993 ◽  
Vol 105 (4) ◽  
pp. 957-963 ◽  
Author(s):  
S.N. Yao ◽  
K. Kurachi
Keyword(s):  
Gene Transfer ◽  
Muscle Regeneration ◽  
Precursor Cells ◽  
Additional Mechanism ◽  
Myogenic Cells ◽  
Muscle Precursor ◽  
Primary Myoblasts ◽  
Muscle Precursor Cells

Intramuscular implanted myoblasts can fuse with existing myofibers. Here we report that implanted primary myoblasts marked with retroviral transgenes can also persist as muscle precursor cells. These cells can be recovered as viable myoblasts from muscles of recipient mice even months after myoblast implantation, and they can fully resume expression of the transgenes in culture. Upon re-implantation into muscles, they again not only fuse with existing myofibers, but also survive as muscle precursor cells in the tissue. These reserve myogenic cells should be able to contribute to host myofibers in muscle regeneration when the recombinant myofibers are damaged, providing an additional mechanism to maintain a persistent expression of transgenes delivered by myoblast-mediated gene transfer.

Human Muscle Precursor Cells Form Human-Derived Myofibers in Skeletal Muscles of Nonhuman Primates: A Potential New Preclinical Setting to Test Myogenic Cells of Human Origin for Cell Therapy of Myopathies

2020 ◽  
Vol 79 (12) ◽  
pp. 1265-1275
Author(s):  
Daniel Skuk ◽  
Jacques P Tremblay
Keyword(s):  
Muscle Regeneration ◽  
De Novo ◽  
Lymphocytic Infiltration ◽  
Precursor Cells ◽  
Human Muscle ◽  
Myogenic Cells ◽  
Cell Therapies ◽  
Muscle Precursor ◽  
Muscle Precursor Cells

Abstract This study aimed to verify if human myogenic cells could participate in muscle regeneration in macaques. This experimental setting would grant researchers a model that could better evaluate the effects of cell therapies in myopathies with a better translation to human patients. Human muscle precursor cells (MPCs) were cultured in vitro and transduced with ß-galactosidase. The cells were subsequently injected into 1-cm3 muscle regions of 6 macaques immunosuppressed with tacrolimus and dexamethasone. Allogeneic ß-galactosidase+ MPCs were injected in other regions as positive controls. Some cell-grafted regions were electroporated to induce extensive muscle regeneration. MPC-grafted regions were sampled 1 month later and analyzed by histology. There were ß-galactosidase+ myofibers in both the regions grafted with human and macaque MPCs. Electroporation increased the engraftment of human MPCs in the same way as in macaque allografts. The histological analysis (hematoxylin and eosin, CD8, and CD4 immunodetection) demonstrated an absence of cellular rejection in most MPC-grafted regions, as well as minimal lymphocytic infiltration in the regions transplanted with human MPCs in the individual with the lowest tacrolimus levels. Circulating de novo anti-donor antibodies were not detected. In conclusion, we report the successful engraftment of human myogenic cells in macaques, which was possible using tacrolimus-based immunosuppression.

An evaluation of cell separation techniques in a model mixed cell population

1992 ◽  
Vol 102 (4) ◽  
pp. 789-798
Author(s):  
S.J. Murphy ◽  
D.J. Watt ◽  
G.E. Jones
Keyword(s):  
Cell Population ◽  
Cell Separation ◽  
Separation Efficiency ◽  
Neuronal Cell ◽  
Quantitative Measure ◽  
Precursor Cells ◽  
Muscle Fibres ◽  
Myogenic Cells ◽  
Muscle Precursor ◽  
Muscle Precursor Cells

Muscle precursor cells may act not only as a means of inserting normal genes into diseased muscle fibres, in order to correct or alleviate a genetically inherited myopathy, but recent demonstrations have shown they may prove an invaluable tool for the expression of, and systemic dissemination of, non-muscle gene products. If muscle precursor cells are proved to act as such widespread vectors in terms of gene therapy, then it is imperative that methods are properly elucidated to produce large populations of pure viable myogenic cells for such purposes. In the past, many methods of cell separation have been investigated but carry with them the problems of either a lack of myogenic purity of the population or poor percentage recovery of the original cell population. In the present work we have investigated two methods for segregating myogenic from non-myogenic cells and have critically reviewed the efficiency of separation of the two techniques used. To obtain a quantitative measure of separation efficiency, segregation was carried out on a 1:1 mixture of murine C2 myogenic and murine 3T3 fibroblastic cells. To distinguish between C2 and 3T3 cells, the latter were prelabelled with the fluorescent strain carboxyfluorescein diacetate succinimyl ester (CFSE). Once incorporated into the cell, CFSE remains there, thus preventing transfer of the label to C2 cells. Both methods of separation used depend on the affinity of myogenic cells for the monoclonal antibody Mab H28, which specifically binds to the mouse neuronal cell adhesion molecule N-CAM, but differ in that one method, “panning”, completes segregation by adherence of N-CAM positive cells to a dish precoated with secondary IgG antibody whereas in the other separation proceeds by the use of commercially available IgG-coated magnetic beads. Results indicate magnetic bead separation to be more efficient than panning if the beads are precoated with 0.1% gelatin.

Incorporation of donor muscle precursor cells into an area of muscle regeneration in the host mouse

1982 ◽  
Vol 57 (2-3) ◽  
pp. 319-331 ◽  
Author(s):  
D.J. Watt ◽  
K. Lambert ◽  
J.E. Morgan ◽  
T.A. Partridge ◽  
J.C. Sloper
Keyword(s):  
Muscle Regeneration ◽  
Precursor Cells ◽  
Muscle Precursor ◽  
Host Mouse ◽  
Donor Muscle ◽  
Muscle Precursor Cells

scholarly journals Evidence for a myogenic stem cell that is exhausted in dystrophic muscle

2000 ◽  
Vol 113 (12) ◽  
pp. 2299-2308 ◽  
Author(s):  
L. Heslop ◽  
J.E. Morgan ◽  
T.A. Partridge
Keyword(s):  
Skeletal Muscles ◽  
Precursor Cells ◽  
Mdx Mouse ◽  
Muscle Fibres ◽  
Significant Extent ◽  
Dystrophic Muscle ◽  
Myogenic Cells ◽  
Mouse Muscle ◽  
Muscle Precursor ◽  
Muscle Precursor Cells

Injection of the myotoxin notexin, was found to induce regeneration in muscles that had been subjected to 18 Gy of radiation. This finding was unexpected as irradiation doses of this magnitude are known to block regeneration in dystrophic (mdx) mouse muscle. To investigate this phenomenon further we subjected mdx and normal (C57Bl/10) muscle to irradiation and notexin treatment and analysed them in two ways. First by counting the number of newly regenerated myofibres expressing developmental myosin in cryosections of damaged muscles. Second, by isolating single myofibres from treated muscles and counting the number of muscle precursor cells issuing from these over 2 day and 5 day periods. After irradiation neither normal nor dystrophic muscles regenerate to any significant extent. Moreover, single myofibres cultured from such muscles produce very few muscle precursor cells and these undergo little or no proliferation. However, when irradiated normal and mdx muscles were subsequently treated with notexin, regeneration was observed. In addition, some of the single myofibres produced rapidly proliferative muscle precursor cells when cultured. This occurred more frequently, and the myogenic cells proliferated more extensively, with fibres cultured from normal compared with dystrophic muscles. Even after 25 Gy, notexin induced some regeneration but no proliferative myogenic cells remained associated with the muscle fibres. Thus, skeletal muscles contain a number of functionally distinct populations of myogenic cells. Most are radiation sensitive. However, some survive 18 Gy as proliferative myogenic cells that can be evoked by extreme conditions of muscle damage; this population is markedly diminished in muscles of the mdx mouse. A small third population survives 25 Gy and forms muscle but not proliferative myogenic cells.

1071 Muscle regeneration and tracking of human muscle precursor cells by MRI in vivo

2012 ◽  
Vol 11 (1) ◽  
pp. e1071-e1071a
Author(s):  
F. Azzabi ◽  
V. Jovaisaite ◽  
J. Njiwa ◽  
A. Boss ◽  
R. Rudin ◽  
...  
Keyword(s):  
Muscle Regeneration ◽  
Precursor Cells ◽  
Human Muscle ◽  
Muscle Precursor ◽  
Muscle Precursor Cells

204 MUSCLE REGENERATION AND TRACKING OF HUMAN MUSCLE PRECURSOR CELLS BY MRI IN VIVO

2012 ◽  
Vol 187 (4S) ◽  
Author(s):  
Fahd Azzabi ◽  
Virginija Jovaisaite ◽  
Andreas Boss ◽  
Josiane Njiwa ◽  
Markus Rudin ◽  
...  
Keyword(s):  
Muscle Regeneration ◽  
Precursor Cells ◽  
Human Muscle ◽  
Muscle Precursor ◽  
Muscle Precursor Cells
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