Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture.
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ABSTRACT:
SUBMITTER: Nakajima T
PROVIDER: S-EPMC8373964 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Self-renewal of tendons is rare since the vascular formation inside is extremely poor, thus reconstructive surgery using autologous tendons has been often taken place in the case of severe injury. However, the rate of re-injury after surgery is relatively high, and collection of autologous tendons leads muscle weakness which results in prolonged rehabilitation. Here, we introduce the induced pluripotent stem cells (iPSCs)-based technology aiming at developing a new therapeutic option after tendon injury. We derived tenocytes from human iPSCs by recapitulating the normal progression of step-wise narrowing fate decisions in the vertebrate embryo. We used single-cell RNA sequencing to analyze the developmental trajectory of iPSCs-derived tenocytes.
2021-07-19 | GSE156753 | GEO
Project description:Self-renewal of tendons is rare since the vascular formation inside is extremely poor, thus reconstructive surgery using autologous tendons has been often taken place in the case of severe injury. However, the rate of re-injury after surgery is relatively high, and collection of autologous tendons leads muscle weakness which results in prolonged rehabilitation. Here, we introduce the induced pluripotent stem cells (iPSCs)-based technology aiming at developing a new therapeutic option after tendon injury. Firstly, we derived tenocytes from human iPSCs by recapitulating the normal progression of step-wise narrowing fate decisions in the vertebrate embryo. We used single-cell RNA sequencing to analyze the developmental trajectory of iPSCs-derived tenocytes. We then demonstrated that grafting iPSCs-tenocytes contributed to recovery of motor function after Achilles tendon injury in rat via engraftments and paracrine effects. The biomechanical strength of regenerated tendons recovered comparable to that of healthy tendons. We propose that the iPSCs-tenocytes will provide a novel therapeutic option in tendon injury.
2021-07-01 | PXD020887 | JPOST Repository
Project description:Grafting induced pluripotent stem cells-derived tenocytes contribute to recovery of motor function after Achilles tendon rupture in rat [single cell RNAseq]
| PRJNA658973 | ENA
Project description:BackgroundThe purpose of this retrospective study was to clarify the operative outcomes of the side-locking loop suture (SLLS) technique accompanied by autologous semitendinosus tendon grafting for chronic Achilles tendon rupture.MethodsA chart review was conducted of consecutive patients treated with the SLLS technique at our department from 2012 to 2017. Postoperatively, a below-knee splint was applied for 2 weeks in 20 degrees of plantar flexion and then active range of motion exercise was started. Partial weightbearing exercise was allowed at 4 weeks according to patient tolerance, and full weightbearing without crutches was allowed at 8 weeks. The American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale score and the Achilles tendon rupture score (ATRS) were used to evaluate clinical outcomes preoperatively and at the final follow-up.ResultsTen patients (6 men, 4 women) were included in the analysis. Mean AOFAS ankle-hindfoot scale score increased significantly from 64.2 ± 5.6 points preoperatively to 95.0 ± 5.3 points at the final follow-up (P < .001). The mean ATRS also increased significantly from 29.8 ± 4.4 points to 86.2 ± 7.7 points, respectively (P < .001). Mean time between surgery and ability to perform 20 continuous double-leg heel raises of the operated foot was 13.5 ± 3.4 (range 10-18) weeks. One patient complained of postoperative hypoesthesia in the foot, which had spontaneously resolved by 3 months after surgery.ConclusionThe SLLS technique accompanied by autologous semitendinosus tendon grafting provided successful operative outcomes for patients with chronic Achilles tendon rupture regardless of the size of the defect, and thus long-term orthotic use was not needed after surgery.Level of evidenceLevel IV, retrospective case series.
| S-EPMC8564925 | biostudies-literature
Project description:PurposeTo evaluate differences of Achilles tendon (AT) hardness and morphology between asymptomatic tendons in patients with acute AT ruptures on the contralateral side and asymptomatic tendons in healthy people by using computer-assisted quantification on axial-strain sonoelastography (ASE).MethodsThe study consisted of 33 asymptomatic tendons in 33 patients (study group) and 34 tendons in 19 healthy volunteers (control group). All the tendons were examined by both ASE and conventional ultrasound. Computer-assisted quantification on ASE was applied to extract hardness variables, including the mean (Hmean), 20th percentile (H20), median (H50) and skewness (Hsk) of the hardness within tendon, and the ratio of the mean hardness within tendon to that outside tendon (Hratio) and three morphological variables: the thickness (THK), cross-sectional area, and eccentricity (ECC) of tendons.ResultsThe Hmean, Hsk, H20, H50, and Hratio in the proximal third of the tendon body in study group were significantly smaller than those in control group (Hmean: 0.43±0.09 vs 0.50±0.07, p=0.001; Hsk: -0.53±0.51 vs -1.09±0.51, p<0.001; H20: 0.31±0.10 vs 0.40±0.10, p=0.001; H50: 0.45±0.10 vs 0.53±0.08, p<0.001; Hratio: 1.01±0.25 vs 1.20±0.23, p=0.003). The THK and cross-sectional area of tendons in the study group were larger than those in the control group (p<0.05).ConclusionsAs a quantitative objective method, the computer-assisted ASE reveals that the asymptomatic ATs contralateral to acute rupture are softer than those of healthy control group at the proximal third and the asymptomatic tendons in people with rupture history are thicker, larger, and rounder than those of normal volunteers especially at the middle and distal thirds of AT body.
| S-EPMC6304598 | biostudies-literature
Project description:The purpose of this study was to compare the inter-limb joint kinematics, joint moments, muscle forces, and joint reaction forces in patients after an Achilles tendon rupture (ATR) via subject-specific musculoskeletal modeling. Six patients recovering from a surgically repaired unilateral ATR were included in this study. The bilateral Achilles tendon (AT) lengths were evaluated using ultrasound imaging. The three-dimensional marker trajectories, ground reaction forces, and surface electromyography (sEMG) were collected on both sides during self-selected speed during walking, jogging and running. Subject-specific musculoskeletal models were developed to compute joint kinematics, joint moments, muscle forces and joint reaction forces. AT lengths were significantly longer in the involved side. The side-to-side triceps surae muscle strength deficits were combined with decreased plantarflexion angles and moments in the injured leg during walking, jogging and running. However, the increased knee extensor femur muscle forces were associated with greater knee extension degrees and moments in the involved limb during all tasks. Greater knee joint moments and joint reaction forces versus decreased ankle joint moments and joint reaction forces in the involved side indicate elevated knee joint loads compared with reduced ankle joint loads that are present during normal activities after an ATR. In the frontal plane, increased subtalar eversion angles and eversion moments in the involved side were demonstrated only during jogging and running, which were regarded as an indicator for greater medial knee joint loading. It seems after an ATR, the elongated AT accompanied by decreased plantarflexion degrees and calf muscle strength deficits indicates ankle joint function impairment in the injured leg. In addition, increased knee extensor muscle strength and knee joint loads may be a possible compensatory mechanism for decreased ankle function. These data suggest patients after an ATR may suffer from increased knee overuse injury risk.
| S-EPMC7369810 | biostudies-literature
Project description:To date, there is no consensus concerning the treatment of acute Achilles tendon ruptures. Although surgical treatment decreases the risk of a recurrent rupture, it is not without complications. In particular, percutaneous sutures may cause a lesion of the sural nerve. The purpose of this Technical Note is to describe a reliable and reproducible surgical procedure for treating these lesions. The first operative phase consists of an ultrasound detection that makes it possible to identify the tendon extremities and the sural nerve, which is necessary to secure the posterolateral arthroscopic tract as well as to perform the percutaneous suture. The entry point is thus centered on the lesion and placed at a distance from any surrounding nerve risk. The second arthroscopic phase makes it possible to release the tendon lesion, control the transtendon passage of the surgical threads, and evaluate the dynamic contact of the tendon edges. At the end of the intervention, the complete disappearance from the transillumination via the rupture also makes it possible to ensure the disappearance of the tendon gap. Achilles tendon percutaneous sutures after the ultrasound detection and under arthroscopic control thus makes it possible to control the contact of the tendon edges, while at the same time decreasing the risk of a lesion of the sural nerve, with minimal scarring.
| S-EPMC6551569 | biostudies-literature
Project description:ObjectiveProfessional Basketball players are at high risk of Achilles tendon rupture. Despite this, there remains limited research into the factors affecting rehabilitation and the long term outcomes of these players. Our aim is to quantify the effect of a player's Achilles tendon rupture on their post-injury performance, and also to explore for correlations between their recovery timeline and pre-injury characteristics. Creation of an injury timeline of past incidents will allow injured players to better track their progress and also inform them about the probable impact on their careers.HypothesisPlayers with Achilles tendon rupture injury will exhibit decreased performance compared to their pre-injury self and their non-injured peers after recovery.MethodsProfessional basketball players who sustained a unilateral Achilles tendon rupture from 1992 to 2016 were collected. 12 players met our inclusion criteria and their Player Efficiency Ratings (PER) were obtained as primary outcome measures; matched controls were chosen based on the PER, Age and playing position. The players' index season PER was compared against the PER during the 10 games immediately following the players' return and the PER of their post-injury peak performing season. The same data analysis was performed against their control group. To investigate the factors affecting the recovery and long-term consequences of their injury, we correlated the variables of Age, BMI, Time of Injury and pre-injury PER with the player's time to return to play and their post-injury PER.Results2 out of 12 players failed to return to playing in the elite professional league following an Achilles Tendon Rupture, others returned after a mean recovery time of 10 months. When compared to players' index PER, the mean PER reduction during the 10 games immediately following the players' return was 7.15 (P < .000). Players on average took 1.8 seasons to reach their post-injury peak performance, with only 1 player returning to his pre-injury performance. Others suffered a mean PER reduction of 3.5 (P = .004) when compared to their index PER and 5.4 (P = .045) against their matched controls.ConclusionAchilles tendon rupture can be a career-ending injury for professional basketball players. They are expected to miss 10 months for rehabilitation and reach their post-injury peak performance level at the 2nd season back. The post-injury peak performance is significantly worse than the pre-injury level, but is similar to matched non-injured players.
| S-EPMC7327851 | biostudies-literature
Project description:IntroductionVarious impairments such as soleus atrophy and consecutive functional deficits in end-range plantarflexion have been described in surgical repair of acute Achilles tendon rupture. The aim of this study was to assess the functional performance at midterm following open surgical repair.Materials and methodsThis cross-sectional study includes n = 52 patients which were tested on average 3.5 ± 1.4 years postoperatively using three different functional performance tests and patient-reported outcome measures. Two different surgical techniques (anatomical repair = AR vs. conventional repair = CR) were compared in a subanalysis. The testing included isokinetic strength testing, a novel setup of heel-rise testing using a marker-based 3D motion analysis system and a gait analysis.ResultsAt an average 3.5 years post-surgery, there is a persisting deficit in plantarflexion strength of 10.2%. Moreover, analysis of maximum peak torque angle and strength deficits according to the plantarflexion angle revealed that these deficits are not equally distributed across the range of motion. AR results in a significantly smaller deficit at 10° of plantarflexion compared to CR (13.9 vs. 29.9%, p < 0.05). This reflects into the functional performance during different modalities (static vs. dynamic) in this novel method of heel-rise testing.ConclusionIn summary, there are persisting functional deficits at > 3 years following Achilles tendon repair which range from strength deficits to specific impairments of functional performance e.g. during heel rise. Anatomical reconstruction is associated with an improved functional performance potentially due to a more symmetric strength during end-range plantarflexion which transfers into a higher satisfaction during athletic activities.Level of evidenceIII, retrospective cohort study.
| S-EPMC9217896 | biostudies-literature
Project description:Achilles tendon rupture (ATR) remains associated with functional limitations years after injury. Architectural remodeling of the gastrocnemius medialis (GM) muscle is typically observed in the affected leg and may compensate force deficits caused by a longer tendon. Yet patients seem to retain functional limitations during-low-force-walking gait. To explore the potential limits imposed by the remodeled GM muscle-tendon unit (MTU) on walking gait, we examined the contractile behavior of muscle fascicles during the stance phase. In a cross-sectional design, we studied nine former patients (males; age: 45 ± 9 years; height: 180 ± 7 cm; weight: 83 ± 6 kg) with a history of complete unilateral ATR, approximately 4 years post-surgery. Using ultrasonography, GM tendon morphology, muscle architecture at rest, and fascicular behavior were assessed during walking at 1.5 m⋅s-1 on a treadmill. Walking patterns were recorded with a motion capture system. The unaffected leg served as control. Lower limbs kinematics were largely similar between legs during walking. Typical features of ATR-related MTU remodeling were observed during the stance sub-phases corresponding to series elastic element (SEE) lengthening (energy storage) and SEE shortening (energy release), with shorter GM fascicles (36 and 36%, respectively) and greater pennation angles (8° and 12°, respectively). However, relative to the optimal fascicle length for force production, fascicles operated at comparable length in both legs. Similarly, when expressed relative to optimal fascicle length, fascicle contraction velocity was not different between sides, except at the time-point of peak series elastic element (SEE) length, where it was 39 ± 49% lower in the affected leg. Concomitantly, fascicles rotation during contraction was greater in the affected leg during the whole stance-phase, and architectural gear ratios (AGR) was larger during SEE lengthening. Under the present testing conditions, former ATR patients had recovered a relatively symmetrical walking gait pattern. Differences in seen AGR seem to accommodate the profound changes in MTU architecture, limiting the required fascicle shortening velocity. Overall, the contractile behavior of the GM fascicles does not restrict length- or velocity-dependent force potentials during this locomotor task.
| S-EPMC8921480 | biostudies-literature