Background Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secretome has been shown to decrease the apoptosis rate, induce proliferation, and promote production of extracellular matrix (ECM). For clinical translation of secretome-based treatment, characterization of the secretome composition is needed to better understand the induced biological processes and identify potentially effective secretomes. Methods This study aimed to investigate the proteome released by bone marrow-derived MSCs following exposure to a healthy, traumatic, or degenerative human IVD environment by mass spectroscopy and quantitative immunoassay analyses. Exposure of MSCs to the proinflammatory stimulus interleukin 1β (IL-1β) was used as control. Results Compared to MSC baseline secretome, there were 224 significantly up- or downregulated proteins following healthy, 179 following traumatic, 223 following degenerative IVD, and 160 proteins following IL-1β stimulus. Stimulation of MSCs with IVD conditioned media induced a more complex MSC secretome, involving more biological processes, compared to stimulation with IL-1β. The MSC response to stimulation with IVD conditioned medium was dependent on their pathological status. Conclusions The MSC secretome seemed to match the primary need of the IVD: homeostasis maintenance in the case of healthy IVDs, versus immunomodulation, adjustment of ECM synthesis and degradation disbalance, and ECM (re) organization in the case of traumatic and degenerative IVDs. These findings highlight the importance of cell preconditioning in the development of tailored secretome therapies. Graphical abstract The secretome of human bone marrow-derived mesenchymal stromal cells (MSCs) stimulated with intervertebral disc (IVD) conditioned medium was analyzed by proteomic profiling. Depending on the pathological state of the IVD, the MSC secretome protein composition indicated immunomodulatory or anabolic activity of the secretome. These findings may have implications for tailored secretome therapy for the IVD and other tissues.

Background: A third of adults aged 65 years and older fall every year, and falls are a common cause of unintentional injuries. Accurate identification of people at risk of falling is an important step in the implementation of preventive strategies.Objective: Our aim was to investigate the association of fall risk factors with number of reported falls in terms of incidence rate ratios and to develop a fall rate prediction model.Methods: In the randomized controlled trial Swiss CHEF, multiple fall risk variables were assessed in community-dwelling older adults at baseline examination, including age, sex, body mass index, fear of falling, number of falls during the prior 12 months, scores on several physical performance tests, comorbidities, and quality of life. Over the following 6 months, interventions were administered in the form of three home-based exercise programs. Participants were subsequently followed up for another 6 months. Falls were reported prospectively using monthly calendars. Incidence rate ratios were derived via negative binomial regression models. Variable selection for the prediction model was conducted using backward elimination and the least absolute shrinkage and selection operator method; the model with the smallest prediction error was then identified.Results: Associations with the number of reported falls were found for number of prior falls, fear of falling, balance and gait deficits, and quality of life. The final model was derived via backward elimination, and the predictors included were prior number of falls and a measure of fear of falling.Outcome: Number of prior falls and fear of falling can be used as predictors in a personalized fall rate estimate for community-dwelling older adults. Recurrent fallers having experienced four or more falls are especially at risk of falling again.

Background Around a third of adults aged 65 and older fall every year, resulting in unintentional injuries in 30% of the cases. Fractures are a frequent consequence of falls, primarily caused in individuals with decreased bone strength who are unable to cushion their falls. Accordingly, an individual’s number of experienced falls has a direct influence on fracture risk. The aim of this study was the development of a statistical model to predict future fall rates using personalized risk predictors. Methods In the prospective cohort GERICO, several fall risk factor variables were collected in community-dwelling older adults at two time-points four years apart (T1 and T2). Participants were asked how many falls they experienced during 12 months prior to the examinations. Rate ratios for the number of reported falls at T2 were computed for age, sex, reported fall number at T1, physical performance tests, physical activity level, comorbidity and medication number with negative binomial regression models. Results The analysis included 604 participants (male: 122, female: 482) with a median age of 67.90 years at T1. The mean number of falls per person was 1.04 and 0.70 at T1 and T2. The number of reported falls at T1 as a factor variable was the strongest risk factor with an unadjusted rate ratio [RR] of 2.60 for 3 falls (95% confidence interval [CI] 1.54 to 4.37), RR of 2.63 (95% CI 1.06 to 6.54) for 4 falls, and RR of 10.19 (95% CI 6.25 to 16.60) for 5 and more falls, when compared to 0 falls. The cross-validated prediction error was comparable for the global model including all candidate variables and the univariable model including prior fall numbers at T1 as the only predictor. Conclusion In the GERICO cohort, the prior fall number as single predictor information for a personalized fall rate is as good as when including further available fall risk factors. Specifically, individuals who have experienced three and more falls are expected to fall multiple times again. Trial registration ISRCTN11865958, 13/07/2016, retrospectively registered.

No abstract