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.

Bioengineering solutions for ureteric disorders: clinical need, challenges and opportunities.

OBJECTIVES: To summarise the causes of ureteric damage and the current standard of care, discussing the risks and benefits of available therapeutic options. We then focus on the current and future solutions that can be provided by ureteric bioengineering and provide a description of the ideal characteristics of a bioengineered product. METHODS: We performed a literature search in February 2021 in: Google Scholar, Medline, and Web of Science. Three searches were conducted, investigating: (a) the epidemiology of ureteric pathology, (b) the current standard of care, and (c) the state of the art in ureteric bioengineering. RESULTS: The most-common causes of ureteric damage are iatrogenic injury and external trauma. Current approaches to treatment include stent placement or surgical reconstruction. Reconstruction can be done using either urological tissue or segments of the gastrointestinal tract. Limitations include scarring, strictures, and infections. Several bioengineered alternatives have been explored in animal studies, with variations in the choice of scaffold material, cellular seeding populations, and pre-implantation processing. Natural grafts and hybrid material appear to be associated with superior outcomes. Furthermore, seeding of the scaffold material with stem cells or differentiated urothelial cells allows for better function compared to acellular scaffolds. Some studies have attempted to pre-implant the graft in the omentum prior to reconstruction, but this has yet to prove any definitive benefits. CONCLUSION: There is an unmet clinical need for safer and more effective treatment for ureteric injuries. Urological bioengineering is a promising solution in preclinical studies. However, substantial scientific, logistic, and economic challenges must be addressed to harness its transformative potential in improving outcomes.

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.

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.

Exploring the factors associated with the mental health of frontline healthcare workers during the COVID-19 pandemic in Cyprus.

INTRODUCTION: The spread of COVID-19 into a global pandemic has negatively affected the mental health of frontline healthcare-workers. This study is a multi-centre, cross-sectional epidemiological study that uses nationwide data to assess the prevalence of stress, anxiety, depression and burnout among health care workers managing COVID-19 patients in Cyprus. The study also investigates the mechanism behind the manifestation of these pathologies, as to allow for the design of more effective protective measures. METHODS: Data on the mental health status of the healthcare workers were collected from healthcare professionals from all over the nation, who worked directly with Covid patients. This was done via the use of 64-item, self-administered questionnaire, which was comprised of the DASS21 questionnaire, the Maslach Burnout Inventory and a number of original questions. Multivariable logistic regression models were used to investigate factors associated with each of the mental health measures. RESULTS: The sample population was comprised of 381 healthcare professionals, out of which 72.7% were nursing staff, 12.9% were medical doctors and 14.4% belonged to other occupations. The prevalence of anxiety, stress and depression among the sample population were 28.6%, 18.11% and 15% respectively. The prevalence of burnout was 12.3%. This was in parallel with several changes in the lives of the healthcare professionals, including; working longer hours, spending time in isolation and being separated from family. DISCUSSION: This study indicates that the mental health of a significant portion of the nation's workforce is compromised and, therefore, highlights the need for an urgent intervention particularly since many countries, including Cyprus, are suffering a second wave of the pandemic. The identified risk factors should offer guidance for employers aiming to protect their frontline healthcare workers from the negative effects of the COVID-19 pandemic.