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The Development of Macrophage-Mediated Cell Therapy to Improve Skeletal Muscle Function after Injury.

Rybalko V, Hsieh PL, Merscham-Banda M, Suggs LJ, Farrar RP - PLoS ONE (2015)

Bottom Line: A variety of MP phenotypes have been identified and characterized in vitro as well as in vivo.We detected a 15% improvement in specific tension and force normalized to mass after M1 (LPS/IFN-γ) MP transplantation 24 hours post-reperfusion.Interestingly, we found that M0 bone marrow-derived unpolarized MPs significantly impaired muscle function highlighting the complexity of temporally coordinated skeletal muscle regenerative program.

View Article: PubMed Central - PubMed

Affiliation: Department of Kinesiology, The University of Texas at Austin, 1 University Station D3700, Austin, TX 78712, United States of America.

ABSTRACT
Skeletal muscle regeneration following acute injury is a multi-step process involving complex changes in tissue microenvironment. Macrophages (MPs) are one of the key cell types involved in orchestration and modulation of the repair process. Multiple studies highlight the essential role of MPs in the control of the myogenic program and inflammatory response during skeletal muscle regeneration. A variety of MP phenotypes have been identified and characterized in vitro as well as in vivo. As such, MPs hold great promise for cell-based therapies in the field of regenerative medicine. In this study we used bone-marrow derived in vitro LPS/IFN-y-induced M1 MPs to enhance functional muscle recovery after tourniquet-induced ischemia/reperfusion injury (TK-I/R). We detected a 15% improvement in specific tension and force normalized to mass after M1 (LPS/IFN-γ) MP transplantation 24 hours post-reperfusion. Interestingly, we found that M0 bone marrow-derived unpolarized MPs significantly impaired muscle function highlighting the complexity of temporally coordinated skeletal muscle regenerative program. Furthermore, we show that delivery of M1 (LPS/IFN-γ) MPs early in regeneration accelerates myofiber repair, decreases fibrotic tissue deposition and increases whole muscle IGF-I expression.

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Related in: MedlinePlus

Trichrome staining for the evaluation of collagen deposition in gastrocnemius muscles 14 days post-reperfusion treated with saline or 2x106in vitro polarized macrophages 24h after TK-I/R injury.(*) p<0.05 compared to saline; (#) p<0.05 compared to M0D1; n = 3/group; 3 fields of view/animal; values expressed as mean ± SEM; one-way ANOVA, Tukey-HSD post-hoc.
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pone.0145550.g005: Trichrome staining for the evaluation of collagen deposition in gastrocnemius muscles 14 days post-reperfusion treated with saline or 2x106in vitro polarized macrophages 24h after TK-I/R injury.(*) p<0.05 compared to saline; (#) p<0.05 compared to M0D1; n = 3/group; 3 fields of view/animal; values expressed as mean ± SEM; one-way ANOVA, Tukey-HSD post-hoc.

Mentions: Despite modest shifts in larger, more mature fibers, it is difficult to ascribe the enhanced muscle function solely to changes in fiber size (Fig 4B). We performed Masson’s trichrome staining in order to quantify intramuscular collagen deposition, as increased deposition of connective tissue has negative impact on contractile muscle function by decreasing myofiber occupancy. As seen in Fig 5, there is approximately 2-fold increase (16%-19% vs. 9%) in percent area occupied by collagen in saline and M0 treated groups, relative to M1 (LPS/IFN-γ) injected muscles. Overall, M1 (LPS/IFN-γ) MP delivery into TK-injured muscle 24-h post-reperfusion positively impacts histological appearance of muscle tissue as evident by the increases in myofiber diameter and reduced fibrosis.


The Development of Macrophage-Mediated Cell Therapy to Improve Skeletal Muscle Function after Injury.

Rybalko V, Hsieh PL, Merscham-Banda M, Suggs LJ, Farrar RP - PLoS ONE (2015)

Trichrome staining for the evaluation of collagen deposition in gastrocnemius muscles 14 days post-reperfusion treated with saline or 2x106in vitro polarized macrophages 24h after TK-I/R injury.(*) p<0.05 compared to saline; (#) p<0.05 compared to M0D1; n = 3/group; 3 fields of view/animal; values expressed as mean ± SEM; one-way ANOVA, Tukey-HSD post-hoc.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696731&req=5

pone.0145550.g005: Trichrome staining for the evaluation of collagen deposition in gastrocnemius muscles 14 days post-reperfusion treated with saline or 2x106in vitro polarized macrophages 24h after TK-I/R injury.(*) p<0.05 compared to saline; (#) p<0.05 compared to M0D1; n = 3/group; 3 fields of view/animal; values expressed as mean ± SEM; one-way ANOVA, Tukey-HSD post-hoc.
Mentions: Despite modest shifts in larger, more mature fibers, it is difficult to ascribe the enhanced muscle function solely to changes in fiber size (Fig 4B). We performed Masson’s trichrome staining in order to quantify intramuscular collagen deposition, as increased deposition of connective tissue has negative impact on contractile muscle function by decreasing myofiber occupancy. As seen in Fig 5, there is approximately 2-fold increase (16%-19% vs. 9%) in percent area occupied by collagen in saline and M0 treated groups, relative to M1 (LPS/IFN-γ) injected muscles. Overall, M1 (LPS/IFN-γ) MP delivery into TK-injured muscle 24-h post-reperfusion positively impacts histological appearance of muscle tissue as evident by the increases in myofiber diameter and reduced fibrosis.

Bottom Line: A variety of MP phenotypes have been identified and characterized in vitro as well as in vivo.We detected a 15% improvement in specific tension and force normalized to mass after M1 (LPS/IFN-γ) MP transplantation 24 hours post-reperfusion.Interestingly, we found that M0 bone marrow-derived unpolarized MPs significantly impaired muscle function highlighting the complexity of temporally coordinated skeletal muscle regenerative program.

View Article: PubMed Central - PubMed

Affiliation: Department of Kinesiology, The University of Texas at Austin, 1 University Station D3700, Austin, TX 78712, United States of America.

ABSTRACT
Skeletal muscle regeneration following acute injury is a multi-step process involving complex changes in tissue microenvironment. Macrophages (MPs) are one of the key cell types involved in orchestration and modulation of the repair process. Multiple studies highlight the essential role of MPs in the control of the myogenic program and inflammatory response during skeletal muscle regeneration. A variety of MP phenotypes have been identified and characterized in vitro as well as in vivo. As such, MPs hold great promise for cell-based therapies in the field of regenerative medicine. In this study we used bone-marrow derived in vitro LPS/IFN-y-induced M1 MPs to enhance functional muscle recovery after tourniquet-induced ischemia/reperfusion injury (TK-I/R). We detected a 15% improvement in specific tension and force normalized to mass after M1 (LPS/IFN-γ) MP transplantation 24 hours post-reperfusion. Interestingly, we found that M0 bone marrow-derived unpolarized MPs significantly impaired muscle function highlighting the complexity of temporally coordinated skeletal muscle regenerative program. Furthermore, we show that delivery of M1 (LPS/IFN-γ) MPs early in regeneration accelerates myofiber repair, decreases fibrotic tissue deposition and increases whole muscle IGF-I expression.

Show MeSH
Related in: MedlinePlus