Vascularization of Cell-Laden Microfibres by Femtosecond Laser Processing.

To face the increasing demand for organ transplantation, currently the development of tissue engineering appears as the best opportunity to effectively regenerate functional tissues and organs. However, these approaches still face the lack of an efficient method to produce an efficient vascularization system. To answer these issues, the formation of an intra-volume channel within a three-dimensional, scaffold free, mature, and cell-covered collagen microfibre is here investigated through laser-induced cavitation. An intra-volume channel was formed upon irradiation with a near-infrared, femtosecond laser beam, focused with a high numerical aperture lens. The laser beam directly crossed the surface of a dense and living-cell bilayer and was focused behind the bilayer to induce channel formation in the hydrogel core while preserving the cell bilayer. Channel formation was assessed through confocal microscopy. Channel generation inside the hydrogel core was enhanced by the formation of voluminous cavitation bubbles with a lifetime longer than 30 s, which also improved intra-volume channel durability. Twenty-four hours after laser processing, cellular viability dropped due to a lack of sufficient hydration for processing longer than 10 min. However, the processing automation could drastically reduce the cellular mortality, this way enabling the formation of hollowed microfibres with a high density of living-cell outer bilayer.

Incidence, prognostic impact and clinical outcomes of renal impairment in patients with multiple myeloma: a population-based registry.

BACKGROUND: Renal impairment (RI), a severe complication in multiple myeloma (MM), is considered as a poor prognostic factor. Patient survival has increased with the use of novel drugs and autologous stem-cell transplantation (ASCT). However, specific evolution of the incidence of RI in MM and its impact on prognosis remain unclear. METHODS: Using a population-based registry of 1038 newly diagnosed MM in Gironde, France, we evaluated the incidence trends of RI in MM patients and assessed net survival according to factors of interest using Pohar-Perme indicator and excess mortality rate regression. We also reviewed 114 cases of MM with RI to describe their clinical outcomes. RESULTS: In our population-based study, 24.6% of MM patients presented with RI (12.9% required haemodialysis). Median survival time was 21 months in patients with RI versus not reached at 3 years for other patients (P < 0.01). Age >73 years, RI, comorbidities and non-use of drugs or ASCT were associated with excess mortality risk. The effect of RI on excess mortality rates was maximum in the first 6 months after diagnosis. In the observational study, median follow-up time was 22.5 months; factors associated with renal response were haematologic response [odds ratio (OR) 6.81; P < 0.01] and previous chronic kidney disease (OR 0.26; P = 0.04). Factors associated with 1-year overall survival were haematological [hazard ratio (HR) 0.13; P < 0.01] and renal response (HR 0.27; P = 0.03). CONCLUSIONS: RI represents an independent negative prognostic factor in MM in the first 6 months after diagnosis. Renal recovery and haematologic response are the strongest markers associated with patient survival.

Comparison of two strategies based on mammalian target of rapamycin inhibitors in secondary prevention of non-melanoma skin cancer after kidney transplantation, a pilot study.

After kidney transplantation, withdrawal of calcineurin inhibitors (CNI) and conversion to sirolimus (SRL) may reduce the occurrence of new non-melanoma skin cancer (NMSC). Conversely, a reduced CNI exposure with everolimus (EVR) is an alternative strategy that has not been thoroughly evaluated. We retrospectively compared the occurrence of newly diagnosed NMSCs in two cohorts of kidney transplant recipients (KTR) with at least one NMSC: 35 patients were converted to EVR with reduced CNI exposure (CNI/EVR group), whereas 46 patients were converted to SRL in association with mycophenolic acid (MPA) (SRL/MPA group). Two years after conversion, survival free of new NMSC was similar between the two cohorts (p = .37), with 19 KTR (54.3%) in the CNI/EVR group and 22 (47.8%) in the SRL/MPA group being diagnosed of at least one new NMSC. Half of the KTR from both groups showed adverse events, leading to mTORi discontinuation for 37.1% of KTR in the CNI/EVR group and 21.7% in the SRL/MPA group (p = .09). The incidence of rejections was similar between the two groups. In a retrospective cohort of KTR with at least one post-transplant NMSC, the outcome of the patients converted to a CNI/EVR regimen was not different from those converted to a SRL/MPA regimen.

Towards an in vitro model of the glomerular barrier unit with an innovative bioassembly method.

BACKGROUND: The development of an artificial glomerular unit may be pivotal for renal pathophysiology studies at a multicellular scale. Using a tissue engineering approach, we aimed to reproduce in part the specific glomerular barrier architecture by manufacturing a glomerular microfibre (Mf). METHODS: Immortalized human glomerular cell lines of endothelial cells (GEnCs) and podocytes were used. Cells and a three-dimensional (3D) matrix were characterized by immunofluorescence with confocal analysis, Western blot and polymerase chain reaction. Optical and electron microscopy were used to study Mf and cell shapes. We also analysed cell viability and cell metabolism within the 3D construct at 14 days. RESULTS: Using the Mf manufacturing method, we repeatedly obtained a cellularized Mf sorting human glomerular cells in 3D. Around a central structure made of collagen I, we obtained an internal layer composed of GEnC, a newly formed glomerular basement membrane rich in α5 collagen IV and an external layer of podocytes. The cell concentration, optimal seeding time and role of physical stresses were modulated to obtain the Mf. Cell viability and expression of specific proteins (nephrin, synaptopodin, vascular endothelial growth factor receptor 2 (VEGFR2) and von Willebrandt factor (vWF)) were maintained for 19 days in the Mf system. Mf ultrastructure, observed with EM, had similarities with the human glomerular barrier. CONCLUSION: In summary, with our 3D bio-engineered glomerular fibre, GEnC and podocytes produced a glomerular basement membrane. In the future, this glomerular Mf will allow us to study cell interactions in a 3D system and increase our knowledge of glomerular pathophysiology.