How to build an allogeneic hematopoietic cell transplant unit in 2016: Proposal for a practical framework.

Allogeneic hematopoietic cell transplantation is part of the standard of care for many hematological diseases. Over the last decades, significant advances in patient and donor selection, conditioning regimens as well as supportive care of patients undergoing allogeneic hematopoietic cell transplantation leading to improved overall survival have been made. In view of many new treatment options in cellular and molecular targeted therapies, the place of allogeneic transplantation in therapy concepts must be reviewed.

Localized interleukin-12 delivery for immunotherapy of solid tumours.

Interleukin (IL)-12 is the key cytokine in the initiation of a Th1 response and has shown promise as an anti-cancer agent; however, clinical trials involving IL-12 have been unsuccessful due to toxic side-effects. To address this issue, lentiviral vectors were used to transduce tumour cell lines that were injected as an autologous tumour cell vaccine. The focus of the current study was to test the efficacy of this approach in a solid tumour model.

Connexin32-null mice develop demyelinating peripheral neuropathy.

Mutations in the gene encoding the gap junction protein connexin32 (Cx32) cause X-linked Charcot-Marie-Tooth disease (CMTX), a common form of inherited demyelinating peripheral neuropathy. To learn more about the pathogenesis of CMTX, we examined the PNS and CNS of cx32-null mice (cx32-/Y males and cx32-/-females) by light and electron microscopy. These mice develop a progressive demyelinating peripheral neuropathy beginning by 3 months of age, and at all ages, motor fibers are more affected than sensory fibers.

Enhanced secretion of amylase from exocrine pancreas of connexin32-deficient mice.

To determine whether junctional communication between pancreatic acinar cells contributes to their secretory function in vivo, we have compared wild-type mice, which express the gap junctional proteins connexin32 (Cx32) and connexin26, to mice deficient for the Cx32 gene. Pancreatic acinar cells from Cx32 (-/-) mice failed to express Cx32 as evidenced by reverse transcription-PCR and immunolabeling and showed a marked reduction (4.8- and 25-fold, respectively) in the number and size of gap junctions.

Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin40-deficient mice.

Intercellular channels of gap junctions are formed in vertebrates by the protein family of connexins and allow direct exchange of ions, metabolites and second messenger molecules between apposed cells (reviewed in [1-3]). In the mouse, connexin40 (Cx40) protein has been detected in endothelial cells of lung and heart and in certain heart muscle cells: atrial myocytes, cells of the atrial ventricular (AV) node and cells of the conductive myocardium, which conducts impulses from the AV node to ventricular myocyctes [3]. We have generated mice homozygous for targeted disruption of the Cx40 gene (Cx40-/-mice).

High incidence of spontaneous and chemically induced liver tumors in mice deficient for connexin32.

Connexins are subunits of gap junction channels, which mediate the direct transfer of ions, second messenger molecules and other metabolites between contacting cells. Gap junctions are thought to be involved in tissue homeostasis, embryonic development and the control of cell proliferation [1,2]. It has also been suggested that the loss of intercellular communication via gap junctions may contribute to multistage carcinogenesis [3-5].

Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction protein connexin 32.

Mutations affecting the connexin 32 (Cx32) gene are associated with the X-linked form of the hereditary peripheral neuropathy Charcot-Marie-Tooth disease (CMTX). We show that Cx32-deficient mice develop a late-onset progressive peripheral neuropathy with abnormalities comparable to those associated with CMTX, thus providing proof of the critical role of Cx32 in the maintenance of peripheral nerve myelin and an animal model for CMTX. Frequently observed features include abnormally thin myelin sheaths, cellular onion bulb formation reflecting myelin degeneration-induced Schwann cell proliferation, and enlarged periaxonal collars while nerve conductance properties are altered only slightly.

Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice.

The gap junctional protein connexin32 is expressed in hepatocytes, exocrine pancreatic cells, Schwann cells, and other cell types. We have inactivated the connexin32 gene by homologous recombination in the mouse genome and have generated homozygous connexin32-deficient mice that were viable and fertile but weighed on the average approximately 17% less than wild-type controls. Electrical stimulation of sympathetic nerves in connexin32-deficient liver triggered a 78% lower amount of glucose mobilization from glycogen stores, when compared with wild-type liver.