Bilateral primary renal diffuse large B-cell lymphoma: a rare presentation of paediatric renal disease mimicking juvenile nephronophthisis.

A 12-year-old boy presented with a prolonged history of headache, fatigue and hypertension. Initial investigations were consistent with presumed non-oliguric end-stage renal disease, leading to a provisional diagnosis of juvenile nephronophthisis. Subsequent imaging demonstrated bilaterally enlarged kidneys without cystic change. Mutation analysis was negative for nephronophthisis, causing diagnostic uncertainty which prompted renal biopsy. Histology revealed a primary renal diffuse large B-cell lymphoma which was highly responsive to chemotherapy, including the anti-CD20 monoclonal agent, rituximab. Renal function improved during lymphoma treatment, with residual chronic kidney disease stage 3a once chemotherapy was completed. Atypical diagnostic features should always prompt re-evaluation of a patient. In this case, the delayed malignancy diagnosis did not have an adverse effect on patient survival or morbidity. The outcome for primary renal lymphoma (PRL) has improved markedly following the introduction of rituximab.

Genetically-programmed, mesenchymal stromal cell-laden & mechanically strong 3D bioprinted scaffolds for bone repair.

Additive manufacturing processes used to create regenerative bone tissue engineered implants are not biocompatible, thereby restricting direct use with stem cells and usually require cell seeding post-fabrication. Combined delivery of stem cells with the controlled release of osteogenic factors, within a mechanically-strong biomaterial combined during manufacturing would replace injectable defect fillers (cements) and allow personalized implants to be rapidly prototyped by 3D bioprinting. Through the use of direct genetic programming via the sustained release of an exogenously delivered transcription factor RUNX2 (delivered as recombinant GET-RUNX2 protein) encapsulated in PLGA microparticles (MPs), we demonstrate that human mesenchymal stromal (stem) cells (hMSCs) can be directly fabricated into a thermo-sintered 3D bioprintable material and achieve effective osteogenic differentiation. Importantly we observed osteogenic programming of gene expression by released GET-RUNX2 (8.2-, 3.3- and 3.9-fold increases in OSX, RUNX2 and OPN expression, respectively) and calcification (von Kossa staining) in our scaffolds. The developed biodegradable PLGA/PEG paste formulation augments high-density bone development in a defect model (~2.4-fold increase in high density bone volume) and can be used to rapidly prototype clinically-sized hMSC-laden implants within minutes using mild, cytocompatible extrusion bioprinting. The ability to create mechanically strong 'cancellous bone-like' printable implants for tissue repair that contain stem cells and controlled-release of programming factors is innovative, and will facilitate the development of novel localized delivery approaches to direct cellular behaviour for many regenerative medicine applications including those for personalized bone repair.

Photosensitiser-gold nanoparticle conjugates for photodynamic therapy of cancer.

Gold nanoparticles (AuNPs) have been extensively studied within biomedicine due to their biocompatibility and low toxicity. In particular, AuNPs have been widely used to deliver photosensitiser agents for photodynamic therapy (PDT) of cancer. Here we review the state-of-the-art for the functionalisation of the gold nanoparticle surface with both photosensitisers and targeting ligands for the active targeting of cancer cell surface receptors. From the initial use of the AuNPs as a simple carrier of the photosensitiser for PDT, the field has significantly advanced to include: the use of PEGylated modification to provide aqueous compatibility and stealth properties for in vivo use; gold metal-surface enhanced singlet oxygen generation; functionalisation of the AuNP surface with biological ligands to specifically target over-expressed receptors on the surface of cancer cells and; the creation of nanorods and nanostars to enable combined PDT and photothermal therapies. These versatile AuNPs have significantly enhanced the efficacy of traditional photosensitisers for both in vitro and in vivo cancer therapy. From this review it is apparent that AuNPs have an important future in the treatment of cancer.