Treatment of Knee Osteoarthritis with Intraarticular Umbilical Cord-Derived Wharton's Jelly: A Case Report.

We present the case of a 27-year-old male with grade II knee osteoarthritis (OA) that was intraarticularly injected with a 2 mL umbilical cord-derived Wharton's jelly (UC-derived WJ) formulation. The patients' baseline radiographs were taken and baseline numeric pain rating scale (NPRS), knee injury and osteoarthritis outcome score (KOOS), 7-point Likert scale, and a 36-item short form survey (SF-36) were recorded. The NPRS was re-recorded immediately after the injection, and at 24 h, 48 h, 1 week, 6 weeks, and at 3 months follow-up post-injection. The KOOS and 7-point Likert scale was re-recorded at the patients' 1week, 6 week, and 3month follow-up, and SF-36 was re-recorded at 3 months. A final set of X-rays were also performed at 3 months follow-up post-injection. No adverse effects from the injection were reported over the duration of the study. No significant difference nor progression in OA on X-rays compared to baseline was observed. NPRS decreased by 50% and the 7-point Likert scale increased to Extremely Satisfied. KOOS increased overall by 10% and the SF-36 overall change was 25%. These results indicate the potential application of UC-derived WJ in the treatment of knee OA. Larger, long term, non-randomized and randomized control trials are warranted to adequately assess the safety and efficacy of UC-derived WJ and ultimate clinical use.

Evaluation of immediate and short-term efficacy of DualStim therapy with and without intracavernosal umbilical cord-derived Wharton's jelly in patients with erectile dysfunction: Study protocol for a randomized controlled trial.

INTRODUCTION: Erectile dysfunction (ED) affects a significant portion of the United States population and causes negative psychological burdens that affects men and their partner's quality of life and satisfaction. Extracorporeal shock therapy (ESWT) utilizing focused ESWT and radial ESWT in Low-intensity shock wave therapy has been used to treat ED with some success. Wharton's Jelly (WJ) is a biologic substance with large amounts of stem cells, growth factors, cytokines and extracellular components. The use of combined focused and radial ESWT (DualStim therapy) with injected WJ have potential uses in ED that may have advantages over current treatments. MATERIALS: A randomized, single-blinded, controlled clinical trial will be conducted to evaluate the efficacy and safety of DualStim therapy and intracavernosal injection of WJ in moderate to severe ED. A total of 60 patients with moderate to severe ED will be enrolled and treated with DualStim therapy with intracavernosal injection of WJ or saline for a period of 7 weeks. The International Index of Erectile Function - Erectile Function score will be used to gauge the treatment related changes in relation to the subject's baseline. The scores will be recorded at baseline and compared to follow-ups 1,3 and 6 months post-treatment. Any adverse events or severe adverse events will be recorded in the corresponding case report forms. Sexual Encounter Profile, as well as the Global Assessment Questionnaire and the Erection Hardness Score will be used to determine the sexual activity improvement from baseline leading to optimal penetration at follow-ups 1,3 and 6 months post-treatment. DISCUSSION: This clinical trial is one of the first studies to determine the immediate and short-term efficacy of DualStim therapy, with and without intracavernosal injection of formulated umbilical cord-derived WJ to improve and/or restore erectile function in patients with moderate to severe ED. This study will also provide insight into the safety and efficacy of WJ. We anticipate clinically significant improvement in patients suffering from moderate and severe ED treated with DualStim therapy with WJ compared to their baseline and DualStim with saline.

Safety and efficacy of umbilical cord-derived Wharton's jelly compared to hyaluronic acid and saline for knee osteoarthritis: study protocol for a randomized, controlled, single-blind, multi-center trial.

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder in the United States of America (USA) with a fast-rising prevalence. Current treatment modalities are limited, and total knee replacement surgeries have shown disadvantages, especially for grade II/III OA. The interest in the use of biologics, including umbilical cord (UC)-derived Wharton's jelly (WJ), has grown in recent years. The results from a preliminary study demonstrated the presence of essential components of regenerative medicine, namely growth factors, cytokines, hyaluronic acid (HA), and extracellular vesicles, including exosomes, in WJ. The proposed study aims to evaluate the safety and efficacy of intra-articular injection of UC-derived WJ for the treatment of knee OA symptoms. METHODS: A randomized, controlled, single-blind, multi-center, prospective study will be conducted in which the safety and efficacy of intra-articular administration of UC-derived WJ are compared to HA (control) and saline (placebo control) in patients suffering from grade II/III knee OA. A total of 168 participants with grade II or III knee OA on the KL scale will be recruited across 53 sites in the USA with 56 participants in each arm and followed for 1 year post-injection. Patient satisfaction, Numeric Pain Rating Scale, Knee Injury and Osteoarthritis Outcome Score, 36-Item Short Form Survey (SF-36), and 7-point Likert Scale will be used to assess the participants. Physical exams, X-rays, and MRI with Magnetic Resonance Observation of Cartilage Repair Tissue score will be used to assess improvement in associated anatomy. DISCUSSION: The study results will provide valuable information into the safety and efficacy of intra-articular administration of Wharton's jelly for grade II/III knee osteoarthritis. The results of this study will also add to the treatment options available for grade II/III OA as well as help facilitate the development of a more focused treatment strategy for patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04711304 . Registered on January 15, 2021.

Umbilical cord-derived Wharton's jelly for treatment of knee osteoarthritis: study protocol for a non-randomized, open-label, multi-center trial.

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder in the USA, and knee OA has the highest prevalence. Inflammation and decrease in vascularization are key factors in the degeneration of articular cartilage and the associated pain and decrease in function. To combat this process, the use of biologics including umbilical cord-derived Wharton's Jelly (UC-derived WJ) has grown. UC-derived WJ contains large quantities of regenerative factors, including growth factors (GFs), cytokines (CKs), hyaluronic acid (HA), and extracellular vesicles (EVs). The proposed study evaluates the safety and efficacy of intraarticular injection of UC-derived WJ for treatment of knee OA symptoms. METHODS AND ANALYSIS: This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular UC-derived WJ in patients suffering from grade II/III OA will be assessed. Twelve patients with grade II/III OA who meet the inclusion and exclusion criteria will be recruited for this study which will be conducted at up to two sites within the USA. The participants will be followed for 1 s. Participants will be assessed using the Numeric Pain Rating Scale (NPRS), Knee Injury and Osteoarthritis Outcome Score (KOOS), 36-item short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, satisfaction, function, and cartilage regeneration. DISCUSSION: This prospective study will contribute to the limited amount of data on UC-derived WJ, particularly with regard to its safety and efficacy. The outcomes from this study will also lay the groundwork for a large placebo-controlled trial of intraarticular UC-derived WJ for symptomatic knee OA. TRIAL REGISTRATION: ClinicalTrials.gov NCT04719793 . Registered on 22 January 2021.

Umbilical cord-derived Wharton's jelly for regenerative medicine applications.

BACKGROUND: The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton's Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes in these products. The present study reports the development of a novel Wharton's jelly formulation and evaluates the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes. METHODS: Human umbilical cords were obtained from consenting caesarian section donors. The Wharton's jelly was then isolated from the procured umbilical cord and formulated into an injectable form. Randomly selected samples from different batches were analyzed for sterility testing and to quantify the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles. RESULTS: All samples passed the sterility test. Growth factors including IGFBP 1, 2, 3, 4, and 6, TGF-α, and PDGF-AA were detected. Several immunomodulatory cytokines, such as RANTES, IL-6R, and IL-16, were also detected. Pro-inflammatory cytokines MCSFR, MIP-1a; anti-inflammatory cytokines TNF-RI, TNF-RII, and IL-1RA; and homeostatic cytokines TIMP-1 and TIMP-2 were observed. Cytokines associated with wound healing, ICAM-1, G-CSF, GDF-15, and regenerative properties, GH, were also expressed. High concentrations of hyaluronic acid were observed. Particles in the extracellular vesicle size range were also detected and were enclosed by the membrane, indicative of true extracellular vesicles. CONCLUSION: There are numerous growth factors, cytokines, hyaluronic acid, and extracellular vesicles present in the Wharton's jelly formulation analyzed. The amount of these factors in Wharton's jelly is higher compared with other biologics and may play a role in reducing inflammation and pain and augment healing of musculoskeletal injuries.

The effect of rotator cuff tears on surgical outcomes after type II superior labrum anterior posterior tears in patients younger than 50 years.

BACKGROUND: Rotator cuff injury in the setting of type II superior labrum anterior posterior lesions is a common finding. Although predictable surgical outcomes can be expected after type II superior labrum anterior posterior repair, the effect of rotator cuff tears on surgical outcome is unknown. HYPOTHESIS: Rotator cuff tears will not negatively affect surgical outcome of type II superior labrum anterior posterior repairs. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The study group included 93 patients younger than 50 years who underwent arthroscopic type II superior labrum anterior posterior repair and were available for review at a minimum of 2 years after surgery. Group 1 patients were identified as having normal rotator cuffs at the time of repair. Group 2 patients were identified as having rotator cuff injury at the time of repair (either partial-thickness or full-thickness tears). Statistical analysis was performed comparing the postoperative University of California, Los Angeles shoulder scores and overall improvement in University of California, Los Angeles score using the Student t test for significance. RESULTS: Mean follow-up was 2.54 years; 52.7% of patients had evidence of rotator cuff tears at the time of surgery. The mean postoperative University of California, Los Angeles score for group 1 was 32.9 (improvement of 11.0), and the mean postoperative University of California, Los Angeles score for group 2 was 33.3 (improvement of 12.2). There was not a significant difference in any of the outcome measures between groups. CONCLUSION: Predictable short-term surgical results and return to activity can be expected after repair of type II superior labrum anterior posterior lesions in patients younger than 50 years who have coexistent rotator cuff tear. Although cuff lesions did not have a negative effect on the short-term outcome in patients with type II superior labrum anterior posterior lesions, longer-term follow-up is needed to determine natural history of this pathologic condition.

Arthroscopic treatment for synovial chondromatosis of the shoulder.

Synovial chondromatosis of the shoulder is a rare condition. The following is a description of such a case with the presenting symptoms, radiographic features, intraoperative findings, and the arthroscopic technique for treatment of this disease. Loose bodies were found in the long head of the biceps tendon sheath, the subscapularis recess, and throughout the glenohumeral joint, causing erosive damage. We feel that arthroscopy allows for better visualization of the entire glenohumeral joint, including the long head of the biceps tendon sheath and the subscapularis recess, and for ease of loose body removal. Additional advantages of arthroscopy include decreased postoperative pain, early active range of motion, shorter course of rehabilitation, and earlier functional return.