Contribution of extracellular matrix components to the stiffness of skeletal muscle contractures in patients with cerebral palsy

Smith, Lucas; Pichika, Rajeswari; Meza, Rachel; Gillies, Allison R.; Baliki, Marwan N.; Chambers, Henry G.; Lieber, Richard L.

doi:10.1080/03008207.2019.1694011

Cited by 38 publications

(49 citation statements)

References 73 publications

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“…These alterations play an important role in the pathology and clinical representation of CP. For example, higher collagen content in the interstitium of the muscle has been associated with higher stiffness (Smith et al, 2019). On the other hand, SC ablation in a transgenic mouse model showed a reduced serial sarcomere number and low recovery ability after immobilization.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies on adolescents showed that the number of SCs in contractured muscles of patients with CP is decreased in comparison to TD controls (Smith et al, 2013;Dayanidhi et al, 2015;Von Walden et al, 2018;Smith et al, 2019). As SCs are considered to be the source of myonuclei, and the number of nuclei was not found to be altered in CP adolescents, it has been suggested that the reduction in SCs is unlikely to occur at a very young age when different myoblasts fuse with multinucleated fibers (Dayanidhi et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy

et al. 2020

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Cerebral palsy (CP), the single largest cause of childhood physical disability, is characterized firstly by a lesion in the immature brain, and secondly by musculoskeletal problems that progress with age. Previous research reported altered muscle properties, such as reduced volume and satellite cell (SC) numbers and hypertrophic extracellular matrix compared to typically developing (TD) children (>10 years). Unfortunately, data on younger CP patients are scarce and studies on SCs and other muscle stem cells in CP are insufficient or lacking. Therefore, it remains difficult to understand the early onset and trajectory of altered muscle properties in growing CP children. Because muscle stem cells are responsible for postnatal growth, repair and remodeling, multiple adult stem cell populations from young CP children could play a role in altered muscle development. To this end, new methods for studying muscle samples of young children, valid to delineate the features and to elucidate the regenerative potential of muscle tissue, are necessary. Using minimal invasive muscle microbiopsy, which was applied in young subjects under general anaesthesia for the first time, we aimed to isolate and characterize muscle stem cell-derived progenitors of TD children and patients with CP. Data of 15 CP patients, 3-9 years old, and 5 aged-matched TD children were reported. The muscle microbiopsy technique was tolerated well in all participants. Through the explant technique, we provided muscle stem cell-derived progenitors from the Medial Gastrocnemius. Via fluorescent activated cell sorting, using surface markers CD56, ALP, and PDGFRa, we obtained SC-derived progenitors, mesoangioblasts and fibro-adipogenic progenitors, respectively. Adipogenic, skeletal, and smooth muscle differentiation assays confirmed the cell identity and ability to give rise to different cell types after appropriate stimuli. Myogenic differentiation in CP SC-derived progenitors showed enhanced fusion index and altered myotube formation based on MYOSIN HEAVY CHAIN expression, as well as disorganization of nuclear spreading, which were not observed in TD myotubes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy

et al. 2020

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“…In effect, these differences are "hidden" by uniaxial stretch. This could partially explain that differences in longitudinal stiffness between cerebral palsy and healthy muscle cannot be explained by collagen content, quantity, and cross-linking alone (Chapman et al, 2015;Lieber and Fridén, 2019;Smith et al, 2019). Smith et al (2019) discuss these collagen content-passive stiffness correlations and a relatively minor contribution of collagen crosslinking that this observation ".…”

Section: Modeling Uniaxial Versus Biaxial Stretchmentioning

confidence: 97%

“…fibers (Figure 2; Yousefi et al, 2018;Bleiler et al, 2019). This formulation attributes muscle fibers and the ECM as the main load-bearing constituents in passively stretched muscle (Smith et al, 2019).…”

Section: Model Component Parametersmentioning

confidence: 99%

“…Our use of a single modulus term is a simplification of a highly complex combination of ECM collagen amount, type, crosslinking, and crimp. While these each have been studied in regards to tissue stiffness through either experimentation (Smith and Barton, 2014;Chapman et al, 2015;Mohammadkhah et al, 2018;Lieber and Fridén, 2019;Smith et al, 2019) or modeling (Gindre et al, 2013;Bleiler et al, 2019; FIGURE 8 | Parametric study stress-stretch curves for (A) uniaxial stretch and (B) biaxial stretch. Note that for both models (Aligned -solid curves and Disperseddashed curves) they exhibit nearly identical uniaxial behavior for both longitudinal (back curves) and transverse (blue curves), but distinctly different behavior when subject to biaxial stretch, with percentage differences between Aligned and Dispersed shown at λ = 1.3.…”

Section: Constitutive Modeling Of Experimental Datamentioning

confidence: 99%

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Investigating Passive Muscle Mechanics With Biaxial Stretch

Wheatley

2020

Front. Physiol.

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Introduction: The passive stiffness of skeletal muscle can drastically affect muscle function in vivo, such as the case for fibrotic tissue or patients with cerebral palsy. The two constituents of skeletal muscle that dominate passive stiffness are the intracellular protein titin and the collagenous extracellular matrix (ECM). However, efforts to correlate stiffness and measurements of specific muscle constituents have been mixed, and thus the complete mechanisms for changes to muscle stiffness remain unknown. We hypothesize that biaxial stretch can provide an improved approach to evaluating passive muscle stiffness. Methods: We performed planar biaxial materials testing of passively stretched skeletal muscle and identified three previously published datasets of uniaxial materials testing. We developed and employed a constitutive model of passive skeletal muscle that includes aligned muscle fibers and dispersed ECM collagen fibers with a bimodal von Mises distribution. Parametric modeling studies and fits to experimental data (both biaxial and previously published) were completed. Results: Biaxial data exhibited differences in time dependent behavior based on orientation (p < 0.0001), suggesting different mechanisms supporting load in the direction of muscle fibers (longitudinal) and in the perpendicular (transverse) directions. Model parametric studies and fits to experimental data exhibited the robustness of the model (<20% error) and how differences in tissue stiffness may not be observed in uniaxial longitudinal stretch, but are apparent in biaxial stretch. Conclusion: This work presents novel materials testing data of passively stretched skeletal muscle and use of constitutive modeling and finite element analysis to explore the interaction between stiffness, constituent variability, and applied deformation in passive skeletal muscle. The results highlight the importance of biaxial stretch in evaluating muscle stiffness and in further considering the role of ECM collagen in modulating passive muscle stiffness.

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Targeted multifidus muscle activation reduces fibrosis of multifidus muscle following intervertebral disc injury

James,

Ahern,

Goodwin

et al. 2024

Eur Spine J

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Purpose Aerobic exercise produces beneficial outcomes in patients with low back pain and partially attenuates the fibrotic changes to the multifidus in a model of intervertebral disc (IVD) degeneration. More targeted exercise might be required to fully attenuate these fibrotic alterations. This study aimed to investigate whether activation of the multifidus induced by neurostimulation could reduce fibrosis of the multifidus in a model of IVD degeneration in sheep. Methods IVD degeneration was induced in 18 merino sheep via a partial thickness unilateral annulus fibrosus lesion to the L1/2 and L3/4 IVDs. All sheep received an implantable neurostimulation device that provides stimulation of the L2 medial branch of the dorsal ramus. Three months after surgery, the animals were assigned to Injury or Activated groups. Activated animals received neurostimulation and the Injury group received no stimulation. Six months after surgery, the multifidus was harvested at L2 and L4. Van Gieson’s, Sirius Red and immunofluorescence staining for Collagen-I and -III and quantitative PCR was used to examine fibrosis. Muscle harvested from a previous study without IVD injury was used as a control. Results Neurostimulation of the multifidus attenuated IVD degeneration dependent increases in the connective tissue, including Collagen-I but not Collagen-III, compared to the Injury group at L4. No measures of the multifidus muscle at L2, which received no stimulation, differed between the Injury and Activated groups. Conclusions These data reveal that targeted activation of the multifidus muscle attenuates IVD degeneration dependent fibrotic alterations to the multifidus.

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Contribution of extracellular matrix components to the stiffness of skeletal muscle contractures in patients with cerebral palsy

Cited by 38 publications

References 73 publications

Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy

Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy

Investigating Passive Muscle Mechanics With Biaxial Stretch

Targeted multifidus muscle activation reduces fibrosis of multifidus muscle following intervertebral disc injury

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