Cryopreservation of Human Adipose Tissues and Adipose-Derived Stem Cells with DMSO and/or Trehalose: A Systematic Review.

Adipose tissue senescence is implicated as a major player in obesity- and ageing-related disorders. There is a growing body of research studying relevant mechanisms in age-related diseases, as well as the use of adipose-derived stem cells in regenerative medicine. The cell banking of tissue by utilising cryopreservation would allow for much greater flexibility of use. Dimethyl sulfoxide (DMSO) is the most commonly used cryopreservative agent but is toxic to cells. Trehalose is a sugar synthesised by lower organisms to withstand extreme cold and drought that has been trialled as a cryopreservative agent. To examine the efficacy of trehalose in the cryopreservation of human adipose tissue, we conducted a systematic review of studies that used trehalose for the cryopreservation of human adipose tissues and adipose-derived stem cells. Thirteen articles, including fourteen studies, were included in the final review. All seven studies that examined DMSO and trehalose showed that they could be combined effectively to cryopreserve adipocytes. Although studies that compared nonpermeable trehalose with DMSO found trehalose to be inferior, studies that devised methods to deliver nonpermeable trehalose into the cell found it comparable to DMSO. Trehalose is only comparable to DMSO when methods are devised to introduce it into the cell. There is some evidence to support using trehalose instead of using no cryopreservative agent.

Understanding cost-utility analysis studies in the trauma and orthopaedic surgery literature.

Cost-utility analysis (CUA) studies are becoming increasingly important due to the need to reduce healthcare spending, especially in the field of trauma and orthopaedics.There is an increasing need for trauma and orthopaedic surgeons to understand these economic evaluations to ensure informed cost-effective decisions can be made to benefit the patient and funding body.This review discusses the fundamental principles required to understand CUA studies in the literature, including a discussion of the different methods employed to assess the health outcomes associated with different management options and the various approaches used to calculate the costs involved.Different types of model design may be used to conduct a CUA which can be broadly categorized into real-life clinical studies and computer-simulated modelling. We discuss the main types of study designs used within each category. We also cover the different types of sensitivity analysis used to quantify uncertainty in these studies and the commonly employed instruments used to assess the quality of CUAs. Finally, we discuss some of the important limitations of CUAs that need to be considered.This review outlines the main concepts required to understand the CUA literature and provides a basic framework for their future conduct. Cite this article: EFORT Open Rev 2021;6:305-315. DOI: 10.1302/2058-5241.6.200115.

Use of human induced pluripotent stem cells for cartilage regeneration in vitro and within chondral defect models of knee joint cartilage in vivo: a Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic literature review.

BACKGROUND AIMS: Articular cartilage has limited regenerative ability when damaged through trauma or disease. Failure to treat focal chondral lesions results in changes that inevitably progress to osteoarthritis. Osteoarthritis is a major contributor to disability globally, which results in significant medical costs and lost wages every year. Human induced pluripotent stem cells (hiPSCs) have long been considered a potential autologous therapeutic option for the treatment of focal chondral lesions. Although there are significant advantages to hiPSCs over other stem cell options, such as mesenchymal and embryonic stem cells, there are concerns regarding their ability to form bona fide cartilage and their tumorgenicity in vivo. METHODS: The authors carried out a systematic literature review on the use of hiPSCs to produce differentiated progeny capable of producing high-quality cartilage in vitro and regenerate cartilage in osteochondral defects in vivo in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight studies were included in the review that used hiPSCs or their derived progeny in xenogeneic transplants in animal models to regenerate cartilage in osteochondral defects of the knee joint. The in vitro-differentiated, hiPSC-derived and in vivo defect repair ability of the hiPSC-derived progeny transplants were assessed. RESULTS: Most studies reported the generation of high-quality cartilage-producing progeny that were able to successfully repair cartilage defects in vivo. No tumorigenicity was observed. CONCLUSIONS: The authors conclude that hiPSCs offer a valuable source of cartilage-producing progeny that show promise as an effective cell-based therapy in treating focal chondral lesions.

The Effectiveness of Anti-Nerve Growth Factor Monoclonal Antibodies in the Management of Pain in Osteoarthritis of the Hip and Knee: A PRISMA Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of the efficacy of anti-nerve growth factor (NGF) monoclonal antibodies in osteoarthritis pain (hip and knee). DESIGN: Grade the evidence for anti-NGF use. METHODS: An interdisciplinary work group conducted a literature search for anti-NGF use in osteoarthritis. The systematic review was performed in accordance with methods described by the Cochrane collaboration. General inclusion criteria included all osteoarthritis trials studying any monoclonal anti-NGF antibody at any dose/phase. Excluded studies were those where participants received NSAIDs or analgesics other than anti-NGF antibodies. The Jadad Scale score was used to assess the quality of the included studies. RESULTS: Thirteen studies were included in the analysis, involving 8145 participants with a diagnosis of hip and/or knee osteoarthritis. Anti-NGF antibody treatment was associated with a significant improvement in all Western Ontario and McMaster Universities Arthritis Index (WOMAC) indices when compared to placebo. These agents were not associated with a significantly increased incidence of serious adverse events but were associated with significant increases in therapy discontinuation due to adverse events or side effects (e.g., peripheral neuropathy). CONCLUSIONS: Future randomized clinical trials are needed to characterize the overall risk-to-benefit ratio of anti-NGF antibodies in managing pain associated with OA, particularly with long-term use, in order to verify their efficacy and safety in clinical practice.

Mesenchymal stem cell therapy in hypertrophic and keloid scars.

Scars are the normal outcome of wound repair and involve a co-ordinated inflammatory and fibrotic process. When a scar does not resolve, uncontrolled chronic inflammation can persist and elicits excessive scarring that leads to a range of abnormal phenotypes such as hypertrophic and keloid scars. These pathologies result in significant impairment of quality of life over a long period of time. Existing treatment options are generally unsatisfactory, and there is mounting interest in innovative cell-based therapies. Despite the interest in mesenchymal stem cells (MSCs), there is yet to be a human clinical trial that investigates the potential of MSCs in treating abnormal scarring. A synthesis of existing evidence of animal studies may therefore provide insight into the barriers to human application. The aim of this PRISMA systematic review was to evaluate the effectiveness of MSC transplantation in the treatment of hypertrophic and keloid scars in in vivo models. A total of 11 case-control studies were identified that treated a total of 156 subjects with MSCs or MSC-conditioned media. Ten studies assessed hypertrophic scars, and one looked at keloid scars. All studies evaluated scars in terms of macroscopic and histological appearances and most incorporated immunohistochemistry. The included studies all found improvements in the above outcomes with MSC or MSC-conditioned media without complications. The studies reviewed support a role for MSC therapy in treating scars that needs further exploration. The transferability of these findings to humans is limited by factors such as the reliability and validity of the disease model, the need to identify the optimal MSC cell source, and the outcome measures employed.

Distal femoral osteotomy: is internal fixation better than external?

BACKGROUND: Distal femoral osteotomies (DFO) can be used to correct deformities around the knee. Although osteotomies can be fixed with either internal or external fixation techniques, the advantages of one over the other are unclear. QUESTIONS/PURPOSES: We asked whether (1) for both techniques, we could accurately correct the deformities based on our preoperative goals for mechanical axis deviation (MAD) and lateral distal femoral angle (LDFA), and (2) intraoperative times, (3) preoperative and postoperative knee ROM, and (4) complications differed. PATIENTS AND METHODS: We identified 26 patients (34 limbs) who underwent femoral osteotomies. We compared accuracy of correction (based on correction of the MAD and the LDFA), duration of surgery, preoperative and postoperative knee ROM, and complications. The minimum followup was 20 months (mean, 29 months; range, 20-40 months). RESULTS: We achieved the desired MAD within 10 mm of the goal in 18 of 21 limbs with the unilateral frame and in 12 of 13 limbs using fixator-assisted plating. Operative time for fixator-assisted plating was longer (122 ± 34 minutes) than when using a unilateral frame (94 ± 65 minutes). Preoperative and postoperative knee ROMs were similar for both techniques and there were no major complications. CONCLUSIONS: We obtained accurate correction of deformities with both fixation techniques. Our experience suggests the method to be used should be left to the discretion of the surgeon and the needs and wishes of the patient after adequate explanation of the advantages and disadvantages. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.