Innate Inflammatory Cells Are Not Responsible for Early Death of Donor Myoblasts After Myoblast Transfer Therapy

Sammels, Leanne M.; Bosio, Erika; Fragall, Clayton; Grounds, Miranda D.; Rooijen, Nico van; Beilharz, Manfred W.

doi:10.1097/01.tp.0000131150.76841.75

Cited by 35 publications

(35 citation statements)

References 29 publications

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“…However, FISH analysis demonstrated the presence of donor-derived muscle SP or MP cells within the spleen of recipient mdx mice 12 weeks after IV injection. It is unclear by the current analyses whether a proportion of muscle SP and MP cells injected IV undergoes rapid cell death within the first 72 hr with very few cells surviving, as previously reported for muscle cells delivered via IM injection (Beauchamp et al 1999;Sammels et al 2004). Alternatively, it is also possible that freshly isolated, IVinjected muscle SP and MP cells may reside longer than 24 hr in the circulation prior to lodging into other organs.…”

Section: Discussionmentioning

confidence: 62%

Myogenic Potential of Muscle Side and Main Population Cells after Intravenous Injection into Sub-lethally IrradiatedmdxMice

Muskiewicz

Frank

Flint

et al. 2005

J Histochem Cytochem.

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S U M M A R YMuscle side population (SP) cells have demonstrated hematopoietic and myogenic activities in vivo upon intravenous (IV) injection into lethally irradiated mdx mice. In contrast, muscle main population (MP) cells were unable to rescue the bone marrow of lethally irradiated mice and, consequently, their in vivo myogenic potential could not be assessed using this method. In the current study, muscle SP or MP cells derived from syngeneic wild-type male mice were delivered to sub-lethally irradiated mdx female mice by single or serial IV injections. Recipient mice were euthanized 12 weeks after transplantation at which time the quadriceps and diaphragm muscles were analyzed for the presence of donor-derived cells. Mice injected with 10 4 muscle SP cells or with 10 6 MP cells appeared to have similar numbers of dystrophin-positive myofibers containing fused donor nuclei. Analysis of the remaining tissue via real-time quantitative PCR indicated that mice injected with muscle SP cells had a higher percentage of donor-derived Y-DNA in the quadriceps than mice injected with MP cells, suggesting that muscle SP cells may be enriched for progenitors able to engraft dystrophic skeletal muscles from the circulation. Although the overall engraftment did not reach therapeutically significant levels, these results indicate that further optimization of cell delivery techniques may lead to improved efficacy of cellmediated therapy using muscle SP cells.

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Section: Discussionmentioning

confidence: 62%

Myogenic Potential of Muscle Side and Main Population Cells after Intravenous Injection into Sub-lethally IrradiatedmdxMice

Muskiewicz

Frank

Flint

et al. 2005

J Histochem Cytochem.

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“…Cytolytic CD8 + T cells and natural killer cells also infiltrate the pockets of donor cells about the first week to initiate the acute rejection process. Although acquired immune response is an important factor in cell death, the findings of graft rejection after myoblast transplant performed in the muscles of histocompatible or severe combined immunodeficient (SCID) mice or immunosuppressed animals in other studies highlight the importance of other unknown innate factors that are involved in graft rejection [27,28].…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Evaluation of Immunosuppressive Drug Efficacy on Acute Donor Cell Survival

et al. 2006

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Purpose-The therapeutic benefits of cell transplantation may depend on the survival of sufficient numbers of grafted cells. We evaluate four potent immunosuppressive medications aimed at preventing acute donor cell death.Procedures and Results-Embryonic rat H9c2 myoblasts were stably transduced to express firefly luciferase reporter gene (H9c2-Fluc). H9c2-Fluc cells (3 × 10 6 ) were injected into thigh muscles of Sprague-Dawley rats (N = 30) treated with cyclosporine, dexamethasone, mycophenolate mofetil, tacrolimus, or saline from day −3 to day +14. Longitudinal optical bioluminescence imaging was performed over two weeks. Fluc activity was 40.0 ± 12.1% (dexamethasone), 30.5 ± 12.5% (tacrolimus), and 21.5 ± 3.5% (mycophenolate) vs. 12.0 ± 5.0% (control) and 8.3 ± 5.0% (cyclosporine) at day 4 (P < 0.05). However, by day 14, cell signals had decreased drastically to <10% for all groups despite drug therapy.Conclusion-This study demonstrates the ability of optical molecular imaging for tracking cell survival noninvasively and raises important questions with regard to the overall efficacy of immunosuppressives for prolonging transplanted cell survival.

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“…The capacity of skeletal myoblasts to restore dystrophin expression in dystrophic recipients [7,8] or engraft into infarction scars [9] was demonstrated in several animal models, such as mice, dogs and primates [10][11][12][13]. However, the effectiveness of these techniques is hindered by numerous limitations, including minimal distribution of cells after injection [14], immune rejection [15] and poor cell survival [16][17][18][19][20][21][22][23]. A major limitation of cell transplantation remains death of the grafted cells.…”

Section: Introductionmentioning

confidence: 99%

Human muscular fetal cells: a potential cell source for muscular therapies

Hirt‐Burri¹,

Roessingh²,

Scaletta

et al. 2007

Pediatr Surg Int

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Myoblast transfer therapy has been extensively studied for a wide range of clinical applications, such as tissue engineering for muscular loss, cardiac surgery or Duchenne Muscular Dystrophy treatment. However, this approach has been hindered by numerous limitations, including early myoblast death after injection and specific immune response after transplantation with allogenic cells. Different cell sources have been analyzed to overcome some of these limitations. The object of our study was to investigate the growth potential, characterization and integration in vivo of human primary fetal skeletal muscle cells. These data together show the potential for the creation of a cell bank to be used as a cell source for muscle cell therapy and tissue engineering. For this purpose, we developed primary muscular cell cultures from biopsies of human male thigh muscle from a 16-week-old fetus and from donors of 13 and 30 years old. We show that fetal myogenic cells can be successfully isolated and expanded in vitro from human fetal muscle biopsies, and that fetal cells have higher growth capacities when compared to young and adult cells. We confirm lineage specificity by comparing fetal muscle cells to fetal skin and bone cells in vitro by immunohistochemistry with desmin and 5.1H11 antibodies. For the feasibility of the cell bank, we ensured that fetal muscle cells retained intrinsic characteristics after 5 years cryopreservation. Finally, human fetal muscle cells marked with PKH26 were injected in normal C57BL/6 mice and were found to be present up to 4 days. In conclusion we estimate that a human fetal skeletal muscle cell bank can be created for potential muscle cell therapy and tissue engineering.

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Innate Inflammatory Cells Are Not Responsible for Early Death of Donor Myoblasts After Myoblast Transfer Therapy

Abstract: Neutrophils and macrophages do not seem to play a major role in the rapid death of donor myoblasts after transplantation into dystrophic muscle. NK cells similarly seem to have no significant effect, contrary to earlier findings reported by our group.

Cited by 35 publications

References 29 publications

Myogenic Potential of Muscle Side and Main Population Cells after Intravenous Injection into Sub-lethally IrradiatedmdxMice

Myogenic Potential of Muscle Side and Main Population Cells after Intravenous Injection into Sub-lethally IrradiatedmdxMice

Noninvasive Evaluation of Immunosuppressive Drug Efficacy on Acute Donor Cell Survival

Human muscular fetal cells: a potential cell source for muscular therapies

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