Dataset Information

Localized SDF-1? Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury.

ABSTRACT: To examine how the chemotactic agent stromal cell-derived factor-1alpha (SDF-1?) modulates the unique cellular milieu within rotator cuff muscle following tendon injury, we developed an injectable, heparin-based microparticle platform to locally present SDF-1? within the supraspinatus muscle following severe rotator cuff injury. SDF-1? loaded, degradable, N-desulfated heparin-based microparticles were fabricated, injected into a rat model of severe rotator cuff injury, and were retained for up to 7 days at the site. The resultant inflammatory cell and mesenchymal stem cell populations were analyzed compared to uninjured contralateral controls and, after 7 days, the fold-change in anti-inflammatory, M2-like macrophages (CD11b+CD68+CD163+, 4.3X fold-change) and mesenchymal stem cells (CD29+CD44+CD90+, 3.0X, respectively) was significantly greater in muscles treated with SDF-1? loaded microparticles than unloaded microparticles or injury alone. Our results indicate that SDF-1? loaded microparticles may be a novel approach to shift the cellular composition within the supraspinatus muscle and create a more pro-regenerative milieu, which may provide a platform to improve muscle repair following rotator cuff injury in the future.

SUBMITTER: Tellier LE

PROVIDER: S-EPMC6166879 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury.

Tellier L E LE Krieger J R JR Brimeyer A L AL Coogan A C AC Falis A A AA Rinker T E TE Schudel A A Thomas S N SN Jarrett C D CD Willett N J NJ Botchwey E A EA Temenoff J S JS

Regenerative engineering and translational medicine 20180423 2

To examine how the chemotactic agent stromal cell-derived factor-1alpha (SDF-1α) modulates the unique cellular milieu within rotator cuff muscle following tendon injury, we developed an injectable, heparin-based microparticle platform to locally present SDF-1α within the supraspinatus muscle following severe rotator cuff injury. SDF-1α loaded, degradable, N-desulfated heparin-based microparticles were fabricated, injected into a rat model of severe rotator cuff injury, and were retained for up t ...[more]

PMID: 30288396

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Project description:ObjectiveThe purpose of this study was to investigate the effect of hyaluronic acid (HA) in the tendon-bone healing process after rotator cuff repair in a rabbit model.MethodsIn vitro, rat bone marrow stromal cells (rBMSCs) were cultured in media for cartilage-related and inflammation-related gene expression levels examination at 1.0 mg/mL of HA. In vivo, 48 New Zealand white rabbits underwent rotator cuff repair surgery, and they were randomly divided into three groups: (1) control group (n = 16), (2) microfracture (MF) group accepting MF treatment (n = 16) and (3) MF/HA group accepting MF with HA treatment (n = 16). Four rabbits from each group were sacrificed at 6 and 12 weeks postoperatively for histological evaluation and biomechanical testing.ResultsIn vitro experiments reveal that HA significantly decreased inflammation-related mRNA expression (IL-1, TNF?) compared with the control group. At 6 weeks after surgery, there was no significant difference of load-to-failure between groups. At 12 weeks after surgery, the mean failure load of the MF/HA group was significantly higher than that of the control group (100.5 ± 10.1 N vs. 68.0 ± 6.2 N; p = 0.0115). The mean failure load of the MF group appeared higher than that of the control group, whereas there was no significant difference (p > 0.05). Histologically, more chondrocytes were clustered at the tendon-bone interface, and more extracellular matrixes were produced in the MF/HA group. The interface of the MF/HA group appeared similar with the normal tendon-bone interface.ConclusionHA may play a crucial role in the acceleration of tendon-to-bone healing which might be through inhibiting inflammation. Rotator cuff repair using MF along with HA led to better tendon-bone healing and a subsequent increase of biomechanical strength at the repair site.The translational potential of this articleHA injection is very common for patients with rotator cuff disease because of its antiinflammatory action and adhesion prevention preoperatively. The HA injection during surgery provides an antiinflammatory effect during tendon-bone healing process and leads to better tendon-bone healing postoperatively.

Project description:Myosteatosis is the pathological accumulation of lipid that occurs in conjunction with atrophy and fibrosis following skeletal muscle injury or disease. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our goal was to identify biochemical pathways that lead to muscle dysfunction and lipid accumulation in injured rotator cuff muscles, a model that demonstrates severe myosteatosis. Adult rats were subjected to a massive tear to the rotator cuff musculature. After a period of either 0 (healthy control), 10, 30, or 60 days, muscles were prepared for RNA sequencing, shotgun lipidomics, metabolomics, biochemical measures, electron microscopy, and muscle fiber contractility. Following rotator cuff injury, there was a decrease in muscle fiber specific force production that was lowest at 30d. There was a dramatic time dependent increase in triacylglyceride content. Interestingly, genes related to not only triacylglyceride synthesis, but also lipid oxidation were largely downregulated over time. Using bioinformatics techniques, we identified that biochemical pathways related to mitochondrial dysfunction and reactive oxygen species were considerably increased in muscles with myosteatosis. Long chain acyl-carnitines and L-carnitine, precursors to beta-oxidation, were depleted following rotator cuff tear. Electron micrographs showed injured muscles displayed large lipid droplets within mitochondria at early time points, and an accumulation of peripheral segment mitochondria at all time points. Several markers of oxidative stress were elevated following rotator cuff tear. The results from this study suggest that the accumulation of lipid in myosteatosis is not a result of canonical lipid synthesis, but occurs due to decreased lipid oxidation in mitochondria. A failure in lipid utilization by mitochondria would ultimately cause an accumulation of lipid even in the absence of increased synthesis. Further study will identify whether this process is required for the onset of myosteatosis.

Dataset Information

Localized SDF-1? Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury.

Publications

Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury.

Similar Datasets

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