Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes

Osteoarthritis (OA) impacts hundreds of millions of people worldwide, with those affected incurring significant physical and financial burdens. Injuries such as focal defects to the articular surface are a major contributing risk factor for the development of OA. Current cartilage repair strategies are moderately effective at reducing pain but often replace damaged tissue with biomechanically inferior fibrocartilage. Here we describe the development, transcriptomic ontogenetic characterization and quality assessment at the single cell level, as well as the scaled manufacturing of an allogeneic human pluripotent stem cell-derived articular chondrocyte formulation that exhibits long-term functional repair of porcine articular cartilage. These results define a new potential clinical paradigm for articular cartilage repair and mitigation of the associated risk of OA.

Clinical and Pathological Characteristics of Patients With Nonproteinuric Diabetic Nephropathy

IntroductionAs the most common complication of diabetes mellitus (DM), diabetic nephropathy (DN) was initially considered to begin with proteinuria preceding the progression of renal insufficiency. This clinical paradigm has been questioned in the late decades, as many DM patients without proteinuria have progressive renal insufficiency. However, the characteristics of nonproteinuric DN were not fully clear yet.Patients and MethodsA total of 390 patients with renal biopsy-proven DN in our center were retrospectively recruited in the current study. Clinical and histopathological data of the patients were analyzed. We used propensity score-matching methods to address the imbalance of age, sex, and diabetes duration for comparative analyses.ResultsAmong all the renal biopsy-proven DN patients with renal biopsy proven DN, 18 patients were classified as nonproteinuric DN. Compared with 36 propensity score-matched proteinuric DN patients, diabetic retinopathy (DR) was less frequent in nonproteinuric DN patients (38.9% vs. 66.4%, p<0.05). During the follow-up of 24.0 (12.0–42.0) months, the probability of developing the end-stage renal disease (ESRD) was significantly lower in nonproteinuric DN patients than in proteinuric ones in both the propensity score-matched cohort and overall cohort (log-rank test, p<0.001 and p<0.001, respectively).ConclusionsCompared with proteinuric DN patients, DR was less frequent in nonproteinuric DN patients. Nonproteinuric DN patients had better renal outcomes than proteinuric DN patients.

Histological Findings After Aortic Cross-Clamping in Preclinical Animal Models

Spinal cord ischemic injury and paralysis are devastating complications after open surgical repair of thoracoabdominal aortic aneurysms. Preclinical models have been developed to simulate the clinical paradigm to better understand the neuropathophysiology and develop therapeutic treatment. Neuropathological findings in the preclinical models have not been comprehensively examined before. This systematic review studies the past 40 years of the histological findings after open surgical repair in preclinical models. Our main finding is that damage is predominantly in the grey matter of the spinal cord, although white matter damage in the spinal cord is also reported. Future research needs to examine the neuropathological findings in preclinical models after endovascular repair, a newer type of surgical repair used to treat aortic aneurysms.

Executive group coaching: interventions not for the faint of heart

As the world is changing, organisations are changing with it: matrix structures, flat hierarchies, virtual work, and teamwork are becoming the norm. Therefore, the ability of working successfully with others has become increasingly important and effective teamwork is essential to make these new complex organisational structures work. However, as this special issue highlights, there are major challenges in working effectively together in this rapidly changing world. Indeed, teams often do not live up to the promise of faster problem solving or higher levels of innovation. "Turf wars" and broken trust are common. Group coaching interventions can be second to none in creating effective collaboration and a culture of trust. Based on the clinical paradigm, this article outlines competencies and conceptual models that make for successful group coaching. Overall, effective group coaching interventions, which will also help executives to lead and direct individual and organisational transformation and to create a coaching culture within organisations, need group coaches who have a holistic orientation and pay attention both to micro and macro processes.

Voluntary exercise in mesothelioma: effects on tumour growth and treatment response in a murine model

Objective There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogen–induced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease development. However, there are limited studies investigating the ability of exercise to prevent or delay cancer, and exercise as a preventive strategy has never been assessed in models with a known carcinogen. We investigated the potential of voluntary exercise (VE) to delay development of asbestos related disease (ARD) in our well-characterised, asbestos induced MexTAg model of mesothelioma. Results Asbestos exposed MexTAg mice were given continuous or delayed access to VE and ARD assessed over time. We found that the addition of VE did not affect ARD development in asbestos exposed MexTAg mice. However, non–asbestos exposed, aged matched control mice participated in significantly more VE behaviours, suggesting subclinical development of ARD after asbestos exposure had a greater impact on VE participation than age alone. These data highlight the importance of model choice and the potential limitation that some pre–clinical studies may not accurately represent the clinical paradigm, particularly in the context of prevention studies.