Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes

Autologous chondrocyte implantation (ACI) is a procedure used to treat articular cartilage injuries and prevent the onset of post-traumatic osteoarthritis. In vitro expansion of chondrocytes, a necessary step in ACI, results in the generation of senescent cells that adversely affect the quality and quantity of newly formed cartilage. Recently, a senolytic peptide, fork head box O transcription factor 4-D-Retro-Inverso (FOXO4-DRI), was reported to selectively kill the senescent fibroblasts. In this study, we hypothesized that FOXO4-DRI treatment could remove the senescent cells in the expanded chondrocytes, thus enhancing their potential in generating high-quality cartilage. To simulate the in vitro expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation. Cells at PDL3 were also used to serve as the minimally expanded control. Results showed that the treatment of FOXO4-DRI removed more than half of the cells in PDL9 but did not significantly affect the cell number of PDL3 chondrocytes. Compared to the untreated control, the senescence level in FOXO4-DRI treated PDL9 chondrocytes was significantly reduced. Based on the result from standard pellet culture, FOXO4-DRI pre-treatment did not enhance the chondrogenic potential of PDL9 chondrocytes. However, the cartilage tissue generated from FOXO4-DRI pretreated PDL9 cells displayed lower expression of senescence-relevant secretory factors than that from the untreated control group. Taken together, FOXO4-DRI is able to remove the senescent cells in PDL9 chondrocytes, but its utility in promoting cartilage formation from the in vitro expanded chondrocytes needs further investigation.

A clinical study focusing Evaluation and treatment of acute and chronic cartilage injuries of the knee

Treatment of articular cartilage injuries have been a challenge for orthopedic surgeons for decades. The following study protocol add knowledge about ongoing research in the field and outline the ongoing long-term follow-up on the transplantation of bone marrow derived stem cells in a clinical trial with 10 years follow-up. The study protocol describes a method to save chondral fractures, which in the past frequently treated with removal of the detached fragments.

The treatment of articular cartilage injuries with mesenchymal stem cells in different animal species

One of the major problems observed in veterinary practice is articular cartilage injuries in animals. In terms of agriculture, it leads to their culling from the herd, even if they are highly productive animals. With companion animals, owners usually have to decide between euthanasia or long-term sometimes lifelong treatment of the injury by a veterinarian. The use of mesenchymal stem cells (MSCs) for the treatment of cartilage injury in veterinary medicine is based on the good results observed in preclinical studies, where large animals have been used as experimental models to study the regenerative activity of MSCs. According to the literature, MSCs in veterinary medicine have been used to treat cartilage injury of dogs and horses, whereas sheep and goats are generally models for reproducing the disease in preclinical experimental studies.

What Are the Predictors of Poor Patient-Reported Outcomes After Shoulder Instability Surgery?

Background: Prospectively collected responses to Patient Acceptable Symptom State (PASS) questions after shoulder instability surgery are limited. Responses to these outcome measures are imperative to understanding their clinical utility. Purpose/Hypothesis: The purpose of this study was to evaluate which factors predict unfavorable patient-reported outcomes after shoulder instability surgery, including “no” to the PASS question. We hypothesized that poor outcomes would be associated with male adolescents, bone loss, combined labral tears, and articular cartilage injuries. Study Design: Cohort study; Level of evidence, 2. Methods: Patients aged ≥13 years undergoing shoulder instability surgery were included in point-of-care data collection at a single institution across 12 surgeons between 2015 and 2017. Patients with anterior-inferior labral tears were included, and those with previous ipsilateral shoulder surgery were excluded. Demographics, American Shoulder and Elbow Surgeons (ASES) and Single Assessment Numeric Evaluation (SANE) scores, and surgical findings were obtained at baseline. ASES and SANE scores, PASS responses, and early revision surgery rates were obtained at a minimum of 1 year after the surgical intervention. Regression analyses were performed. Results: A total of 234 patients met inclusion criteria, of which 176 completed follow-up responses (75.2%). Nonresponders had a younger age, greater frequency of glenoid bone loss, fewer combined tears, and more articular cartilage injuries ( P < .05). Responders’ mean age was 25.1 years, and 22.2% were female. Early revision surgery occurred in 3.4% of these patients, and 76.1% responded yes to the PASS question. A yes response correlated with a mean 25-point improvement in the ASES score and a 40-point improvement in the SANE score. On multivariate analysis, combined labral tears (anterior-inferior plus superior or posterior tears) were associated with greater odds of responding no to the PASS question, while both combined tears and injured capsules were associated with lower ASES and SANE scores ( P < .05). Sex, bone loss, and grade 3 to 4 articular cartilage injuries were not associated with variations on any patient-reported outcome measure. Conclusion: Patients largely approved of their symptom state at ≥1 year after shoulder instability surgery. A response of yes to the PASS question was given by 76.1% of patients and was correlated with clinically and statistically significant improvements in ASES and SANE scores. Combined labral tears and injured capsules were negative prognosticators across patient-reported outcome measures, whereas sex, bone loss, and cartilage injuries were not.

Measuring Outcomes in Knee Articular Cartilage Pathology

Measuring outcomes following treatment of knee articular cartilage lesions is crucial to determine the natural history of disease and the efficacy of treatments. Outcome assessments for articular cartilage treatments can be clinical (based on failure, lack of healing, reoperation, need for arthroplasty), radiographic (X-ray, MRI), histologic, or patient reported and functional. The purpose of this review is to discuss the application and properties of patient-reported outcomes (PROs) with a focus on articular cartilage injuries and surgery in the knee. The most frequently used and validated PROs for knee articular cartilage studies include: the Knee injury and Osteoarthritis and Outcome Score, International Knee Documentation Committee Subjective Knee Form, and Lysholm score as knee-specific measures; the Marx Activity Rating Scale and Tegner Activity Scale as activity measures; and EQ-5D and SF-36/12 as generic quality-of-life measures. Incorporating these validated PROs in studies pertaining to knee articular cartilage lesions will allow researchers to fully capture clinically relevant outcomes that are most important to patients.