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Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_16 | Pages 32 - 32
1 Oct 2016
Hamilton D Gaston P Simpson A
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Physical outcome following total knee arthroplasty is variable. Satellite cells are undifferentiated myogenic precursors considered to be muscle stem cells. We hypothesised that; the recovery of muscle strength and physical function following knee arthroplasty would be influenced by the underlying number of muscle satellite cells. 16 patients provided a distal quadriceps muscle biopsy at time of surgery. Satellite cells were identified with a primary mouse antibody for Pax7 – a cytoplasmic protein marker, and the myonuclei with DAPI. Positive cells were identified on the basis of immunofluorescent staining in association with nuclear material, and confirmed by position under the basal lamina. Patient function was assessed using a validated physical assessment protocol, the Aggregated Locomotor Function (ALF) score, muscle strength assessed using the leg extensor power-rig, and clinical outcome assessed with the Oxford Knee Score (OKS) pre-operatively and at 1 year post operatively. Muscle satellite cell content varied amongst the patient group (Positive Staining Index 3.1 to 11.4). Satellite cell content at time of surgery correlated with change in outcomes between pre-operative and 1 year assessments in all assessed parameters (ALF, r = 0.31; muscle power, r = 49; OKS, r = 0.33). Regression analysis employing a forward stepwise selection technique employed satellite cell volume in models of pre-operative to 1 year change for all outcome parameters. Physical function (satellite cell content, patient age and pre-operative ALF score) adjusted R2 = 0.92; Muscle power (pre-operative power and satellite cell content) adjusted R2 = 0.38; Clinical outcome (pre-operative OKS and satellite cell content) adjusted R2 = 0.28. Muscle satellite cell content influences recovery of muscle power and physical function following total knee arthroplasty. Importantly it is also associated with change in clinical scores; suggesting it to be a biomarker for patient outcomes


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 22 - 22
1 May 2012
Hamilton D Gaston P Simpson A
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Introduction. Recovery of muscle strength following Total Knee Replacement (TKR) is variable, and can affect the resultant function of the patient. Satellite cells are undifferentiated myogenic precursors considered to be muscle stem cells that lie quiescently around the muscle fibre. These cells repair damaged fibres and have the potential to generate new muscle fibres. Therefore, theoretically, they could be associated with the variation in muscle recovery following surgery. We hypothesised that the recovery of muscle strength following knee replacement in a given patient would be influenced by the underlying number of satellite cells in that patient. Methods. 20 patients undergoing TKR were recruited from the waiting list of a single consultant. A muscle biopsy was taken at the time of surgery from the distal quadriceps. This was fixed in paraffin wax, and sections obtained. Satellite cells were identified with a primary mouse antibody for Pax7 - a cytoplasmic protein marker - and an immunofluorescent goat anti-mouse secondary. Slides were counterstained with DAPI to stain the myonuclei. The positive staining index (PSI) was calculated (number of satellite cells/total number of myonuclei x 100). Recovery of muscle (quadriceps) strength was assessed using the leg extensor power-rig (LegRig) pre-operatively, at 6 and 26 weeks post-operatively. Statistical analysis was performed using the Minitab version 15 software, the level of significance was set as p = 0.05. Results. 3 patients were unable to provide follow-up data. The number of satellite cells amongst individual patients in our cohort varied (PSI 3.07 to 11.35). Improvement in muscle power post-op also varied (0 to 70 W) between the 6 and 26 weeks assessment periods. This improvement in wattage generated between assessments reflected a relative improvement of between 0 and 60% in the strength to bodyweight ratio of these patients. The improvement in muscle power correlated with the satellite cell numbers (determined at the time of surgery). This was true for both absolute improvement in wattage generated (r = 0.54 p= 0.038) and also the improvement in strength to body weight ratio (r = 0.47 p = 0.06). Linear regression analysis demonstrated that the relative satellite cell number accounted for 30% of the improvement in muscle power. Discussion. We have for the first time demonstrated that the magnitude of improvement in muscle strength following TKR may be influenced by the patient's underlying pool of muscle satellite cells, with up to 30% of the variation of improvement in our cohort attributable to the satellite cell population


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 12 | Pages 1666 - 1669
1 Dec 2006
Shisha T Kiss S Pap K Simpson H Szöke G

The response of the muscle is critical in determining the functional outcome of limb lengthening. We hypothesised that muscle response would vary with age and therefore studied the response of the muscles during tibial lengthening in ten young and ten mature rabbits. A bromodeoxyuridine technique was used to identify the dividing cells.

The young rabbits demonstrated a significantly greater proliferative response to the distraction stimulus than the mature ones. This was particularly pronounced at the myotendinous junction, but was also evident within the muscle belly.

Younger muscle adapted better to lengthening, suggesting that in patients in whom a large degree of muscle lengthening is required it may be beneficial to carry out this procedure when they are young, in order to achieve the optimal functional result.


Bone & Joint Research
Vol. 3, Issue 9 | Pages 262 - 272
1 Sep 2014
Gumucio J Flood M Harning J Phan A Roche S Lynch E Bedi A Mendias C

Objectives

Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as ‘fatty degeneration’. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified.

Methods

A full-thickness, massive supraspinatus and infraspinatus tear was induced in adult T-cell deficient rats. We hypothesised that, compared with controls, 28 days after inducing a tear we would observe a decrease in muscle force production, an accumulation of type IIB fibres, and an upregulation in the expression of genes involved with muscle atrophy, fibrosis and inflammation.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 6 | Pages 894 - 899
1 Jun 2010
Khattak MJ Ahmad T Rehman R Umer M Hasan SH Ahmed M

The nervous system is known to be involved in inflammation and repair. We aimed to determine the effect of physical activity on the healing of a muscle injury and to examine the pattern of innervation. Using a drop-ball technique, a contusion was produced in the gastrocnemius in 20 rats. In ten the limb was immobilised in a plaster cast and the remaining ten had mobilisation on a running wheel. The muscle and the corresponding dorsal-root ganglia were studied by histological and immunohistochemical methods.

In the mobilisation group, there was a significant reduction in lymphocytes (p = 0.016), macrophages (p = 0.008) and myotubules (p = 0.008) between three and 21 days. The formation of myotubules and the density of nerve fibres was significantly higher (both p = 0.016) compared with those in the immobilisation group at three days, while the density of CGRP-positive fibres was significantly lower (p = 0.016) after 21 days.

Mobilisation after contusional injury to the muscle resulted in early and increased formation of myotubules, early nerve regeneration and progressive reduction in inflammation, suggesting that it promoted a better healing response.