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Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture.

ABSTRACT: Tendon self-renewal is a rare occurrence because of the poor vascularization of this tissue; therefore, reconstructive surgery using autologous tendon is often performed in severe injury cases. However, the post-surgery re-injury rate is relatively high, and the collection of autologous tendons leads to muscle weakness, resulting in prolonged rehabilitation. Here, we introduce an induced pluripotent stem cell (iPSC)-based technology to develop a therapeutic option for tendon injury. First, we derived tenocytes from human iPSCs by recapitulating the normal progression of step-wise narrowing fate decisions in vertebrate embryos. We used single-cell RNA sequencing to analyze the developmental trajectory of iPSC-derived tenocytes. We demonstrated that iPSC-tenocyte grafting contributed to motor function recovery after Achilles tendon injury in rats via engraftment and paracrine effects. The biomechanical strength of regenerated tendons was comparable to that of healthy tendons. We suggest that iPSC-tenocytes will provide a therapeutic option for tendon injury.

SUBMITTER: Nakajima T

PROVIDER: S-EPMC8373964 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture.

Nakajima Taiki T Nakahata Akihiro A Yamada Naoki N Yoshizawa Keiko K Kato Tomoaki M TM Iwasaki Mio M Zhao Chengzhu C Kuroki Hiroshi H Ikeya Makoto M

Nature communications 20210818 1

Tendon self-renewal is a rare occurrence because of the poor vascularization of this tissue; therefore, reconstructive surgery using autologous tendon is often performed in severe injury cases. However, the post-surgery re-injury rate is relatively high, and the collection of autologous tendons leads to muscle weakness, resulting in prolonged rehabilitation. Here, we introduce an induced pluripotent stem cell (iPSC)-based technology to develop a therapeutic option for tendon injury. First, we de ...[more]

PMID: 34408142

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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.

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.

Dataset Information

Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture.

Publications

Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture.

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