The Effects of Chronological Age on the Chondrogenic Potential of Mesenchymal Stromal Cells: A Systematic Review.

Tissue engineering and cell therapy for regenerative medicine have great potential to treat chronic disorders. In musculoskeletal disorders, mesenchymal stromal cells (MSCs) have been identified as a relevant cell type in cell and regenerative strategies due to their multi-lineage potential, although this is likely to be a result of their trophic and immunomodulatory effects on other cells. This PRISMA systematic review aims to assess whether the age of the patient influences the chondrogenic potential of MSCs in regenerative therapy. We identified a total of 3027 studies after performing a search of four databases, including Cochrane, Web of Science, Medline, and PubMed. After applying inclusion and exclusion criteria, a total of 14 papers were identified that were reviewed, assessed, and reported. Cell surface characterization and proliferation, as well as the osteogenic, adipogenic, and chondrogenic differentiation, were investigated as part of the analysis of these studies. Most included studies suggest a clear link between aged donor MSCs and diminished clonogenic and proliferative potential. Our study reveals a heterogeneous and conflicting range of outcomes concerning the chondrogenic, osteogenic, and adipogenic potential of MSCs in relation to age. Further investigations on the in vitro effects of chronological age on the chondrogenic potential of MSCs should follow the outcomes of this systematic review, shedding more light on this complex relationship.

Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis.

OBJECTIVES: The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF). METHODS: In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end-to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables, and lung function tests. Univariable and multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern, and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT. RESULTS: No significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced intersegmental tapering, and increased segmental tortuosity associated with increased risk of death. On multivariable Cox analyses (adjusted using FVC), intersegmental tapering (hazard ratio (HR) = 0.75, 95% CI = 0.66-0.85, p < 0.001) and segmental tortuosity (HR = 1.74, 95% CI = 1.22-2.47, p = 0.002) independently associated with mortality. Results were maintained with adjustment using DLco. CONCLUSIONS: AirQuant generated measures of intersegmental tapering and segmental tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value. CLINICAL RELEVANCE STATEMENT: Quantitative measurements of intersegmental tapering and segmental tortuosity, in proximal (second to sixth) generation airway segments, independently associate with mortality in IPF. Automated airway analysis can estimate disease severity, which in IPF is not restricted to the distal airway tree. KEY POINTS: • AirQuant generates measures of intersegmental tapering and segmental tortuosity. • Automated airway quantification associates with mortality in IPF independent of established measures of disease severity. • Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF.

Bullying, harassment, and discrimination of musculoskeletal researchers and the impact of the COVID-19 pandemic: an international study.

PURPOSE: Bullying, harassment, and discrimination (BHD) are prevalent in academic, scientific, and clinical departments, particularly orthopedic surgery, and can have lasting effects on victims. As it is unclear how BHD affects musculoskeletal (MSK) researchers, the following study assessed BHD in the MSK research community and whether the COVID-19 pandemic, which caused hardships in other industries, had an impact. METHODS: A web-based anonymous survey was developed in English by ORS Spine Section members to assess the impact of COVID-19 on MSK researchers in North America, Europe, and Asia, which included questions to evaluate the personal experience of researchers regarding BHD. RESULTS: 116 MSK researchers completed the survey. Of respondents, 34.5% (n = 40) focused on spine, 30.2% (n = 35) had multiple areas of interest, and 35.3% (n = 41) represented other areas of MSK research. BHD was observed by 26.7% (n = 31) of respondents and personally experienced by 11.2% (n = 13), with mid-career faculty both observing and experiencing the most BHD. Most who experienced BHD (53.8%, n = 7) experienced multiple forms. 32.8% (n = 38) of respondents were not able to speak out about BHD without fear of repercussions, with 13.8% (n = 16) being unsure about this. Of those who observed BHD, 54.8% (n = 17) noted that the COVID-19 pandemic had no impact on their observations. CONCLUSIONS: To our knowledge, this is the first study to address the prevalence and determinants of BHD among MSK researchers. MSK researchers experienced and observed BHD, while many were not comfortable reporting and discussing violations to their institution. The COVID-19 pandemic had mixed-effects on BHD. Awareness and proactive policy changes may be warranted to reduce/eliminate the occurrence of BHD in this community.

Principles of management of hand fractures.

The optimal management of hand fractures requires a multidisciplinary approach. Initial assessment should include a thorough medical history and clinical examination, followed by appropriate radiological imaging. These are crucial in determining the appropriate management. Following joint stabilisation to allow fractures to unite, early mobilisation is needed to maximise the functional restoration of the hand. In this review, the principles of operative and non-operative management of these injuries are discussed.

Cell-Assisted Lipotransfer in Breast Augmentation Surgery: Clinical Outcomes and Considerations for Future Research.

Autologous fat transfer is a widely used surgical technique, chosen by numerous plastic surgeons for breast augmentation surgery. This technique is based on three steps: 1. harvesting of the lipoaspirate from the patient, 2. centrifugation and removal of the top, oily, layer, and 3. implantation in the patient's breast(s). It has been associated with various complications, including post-surgical fat resorption, as measured quantitatively with MRI, CT, and other 3D-quantification systems. Adipose-derived stem cells have been explored as a means of addressing fat resorption. They can be separated from the lipoaspirate following centrifugation, and enzymatically purified from unwanted debris, with collagenase, forming the stromal vascular fraction. The stromal vascular fraction is then recombined with the graft volume prior to implantation. This novel technique, referred to as "cell-assisted lipotransfer", has shown promising results in terms of reducing fat resorption. These results are due to the pro-angiogenic and pro-adipogenic ability of the stem cells, which allow the graft to address the conditions of ischemia more effectively than autologous fat transfer. The aim of this review is to explore the ways in which cell-assisted lipotransfer is different from the autologous fat transfer, as well as how and why adipose-derived stem cells may contribute towards limiting fat resorption. The immunological background of these cells is discussed in detail, while grounds for further development are discussed, by means of the administration of external growth factors, which could, potentially, maximize outcomes, while limiting complications.

Chronological Age Affects MSC Senescence In Vitro-A Systematic Review.

The use of mesenchymal stromal cells (MSCs) in regenerative medicine and tissue engineering is well established, given their properties of self-renewal and differentiation. However, several studies have shown that these properties diminish with age, and understanding the pathways involved are important to provide regenerative therapies in an ageing population. In this PRISMA systematic review, we investigated the effects of chronological donor ageing on the senescence of MSCs. We identified 3023 studies after searching four databases including PubMed, Web of Science, Cochrane, and Medline. Nine studies met the inclusion and exclusion criteria and were included in the final analyses. These studies showed an increase in the expression of p21, p53, p16, ROS, and NF-κB with chronological age. This implies an activated DNA damage response (DDR), as well as increased levels of stress and inflammation in the MSCs of older donors. Additionally, highlighting the effects of an activated DDR in cells from older donors, a decrease in the expression of proliferative markers including Ki67, MAPK pathway elements, and Wnt/ß-catenin pathway elements was observed. Furthermore, we found an increase in the levels of SA-ß-galactosidase, a specific marker of cellular senescence. Together, these findings support an association between chronological age and MSC senescence. The precise threshold for chronological age where the reported changes become significant is yet to be defined and should form the basis for further scientific investigations. The outcomes of this review should direct further investigations into reversing the biological effects of chronological age on the MSC senescence phenotype.