An alginate-based encapsulation system for delivery of therapeutic cells to the CNS

Treatment options for neurodegenerative conditions such as Parkinson''s disease have included the delivery of cells which release dopamine or neurotrophic factors to the brain. Here, we report the development of a novel approach for protecting cells after implantation into the central nervous system (CNS), by developing dual-layer alginate beads that encapsulate therapeutic cells and release an immunomodulatory compound in a sustained manner. An optimal alginate formulation was selected with a view to providing a sustained physical barrier between engrafted cells and host tissue, enabling exchange of small molecules while blocking components of the host immune response. In addition, a potent immunosuppressant, FK506, was incorporated into the outer layer of alginate beads using electrosprayed poly-ε-caprolactone core–shell nanoparticles with prolonged release profiles. The stiffness, porosity, stability and ability of the alginate beads to support and protect encapsulated SH-SY5Y cells was demonstrated, and the release profile of FK506 and its effect on T-cell proliferation in vitro was characterized. Collectively, our results indicate this multi-layer encapsulation technology has the potential to be suitable for use in CNS cell delivery, to protect implanted cells from host immune responses whilst providing permeability to nutrients and released therapeutic molecules.

Novel composite cell encapsulation system: dual-layer, micro-scale beads maintain cell survival while releasing immunomodulatory FK506 in a sustained manner. This biotechnology platform could be applicable for treatment of CNS and other disorders.     

Right ventricular outflow tract obstruction caused by a right coronary cusp prolapse: An unusual finding

Patients with large sub-pulmonic ventricular septal defect (VSD) present early as a results of their complications. Some present late, due to the restriction of VSD by the right coronary cusp (RCC) due to its prolapse. In this report, we present a rare case of sub-pulmonic VSD in a 33-year-old man who developed a sub-pulmonic stenosis due to the prolapse of the RCC into the right ventricular outflow tract.     

Unexpected mechanism of mitral regurgitation in a patient post ALCAPA repair: Added value of three-dimensional echocardiography

Accurate assessment of etiology of mitral regurgitation (MR) is one of the key steps in the decision-making process and further clinical management of patients with severe MR. Our clinical case illustrates the added value of three-dimensional echocardiography (3DE) in assessment of mitral valve morphology and identification of an unexpected mechanism of MR which was not previously diagnosed using conventional echocardiography. 3DE helped to choose appropriate management strategy in this patient.     

Epstein-Barr virus lymphoproliferation after bone marrow transplantation

We review 15 cases of secondary B-cell lymphoproliferative disorders that occurred among 2,475 patients who received allogeneic bone marrow transplants (BMTs) at the Fred Hutchinson Cancer Research Center (Seattle) between 1969 and 1987. The histopathologic findings in 14 of the 15 patients spanned a wide spectrum of lymphoproliferative lesions. One patient had features characteristic of angioimmunoblastic lymphadenopathy. Epstein-Barr virus (EBV) genomic sequences were identified by Southern blot analysis in each of the 13 patients evaluated. Ten of the 12 lesions evaluated originated in donor cells. In two patients, who had mixed chimerism after transplantation, the lesions originated in host cells. The combined evidence from immunoglobulin light chain staining and the analysis of immunoglobulin heavy chain gene rearrangement indicated that the lesions in most patients represented polyclonal proliferations that gave rise to clonal subpopulations. The results indicate an overall actuarial incidence of 0.6% for this complication in BMT recipients. Anti-CD3 monoclonal antibody (MoAb) treatment of acute graft-v-host disease (GVHD) and T cell depletion of the donor marrow were statistically significant risk factors, and GVHD appeared to play a contributing role, particularly in the setting of human leukocyte antigen (HLA) disparity. Two patients had no identifiable risk factors. Prophylaxis or treatment with acyclovir had no detectable effect in the patients; all but two died with uncontrolled lymphoproliferation.