Paola Quaranta

Mesenchymal Stem Cells Prevent Acute Rejection and Prolong Graft Function in Pancreatic Islet Transplantation

BACKGROUND Pancreatic islet transplantation is a promising cell-based therapy for type 1 diabetes (insulin-dependent diabetes mellitus), a disease triggered by the immune response against autoantigens of beta-cells. However, the recurrence of immune response after transplantation and the diabetogenic and growth-stunting side effects of immunosuppressants are major challenges to the application of islet transplantation. Mesenchymal stem cells (MSCs) have recently been reported to modulate the immune response in allogeneic transplantation. METHODS The ability of MSCs, either syngeneic or allogeneic to recipients, to prevent acute rejection and improve glycemic control was investigated in rats with diabetes given a marginal mass of pancreatic islets through the portal vein. RESULTS Reduced glucose levels and low-grade rejections were observed up to 15 days after transplantation upon triple-dose administration of MSCs, indicating that MSCs prolong graft function by preventing acute rejection. The efficacy of MSCs was associated with a reduction of pro-inflammatory cytokines and was independent of the administration route. Efficacy was similar for MSCs whether syngeneic or allogeneic to recipients and comparable to that of immunosuppressive therapy. CONCLUSIONS The results show that MSCs modulate the immune response through a down-regulation of pro-inflammatory cytokines, suggesting that MSCs may prevent acute rejection and improve graft function in portal vein pancreatic islet transplantation.

Magnetic carbon nanotubes: a new tool for shepherding mesenchymal stem cells by magnetic fields.

AIMS We investigated the interaction between magnetic carbon nanotubes (CNTs) and mesenchymal stem cells (MSCs), and their ability to guide these intravenously injected cells in living rats by using an external magnetic field. MATERIALS & METHODS Multiwalled CNTs were used to treat MSCs derived from rat bone marrow. Cytotoxicity induced by nanotubes was studied using the WST-1 proliferation and Hoechest 33258 apoptosis assays. The effects of nanotubes on MSCs were evaluated by monitoring the effects on cellular growth rates, immunophenotyping and differentiation, and on the arrangement of cytoskeletal actin. MSCs loaded with nanotubes were injected in vivo in the portal vein of rats driving their localization in the liver by magnetic field. An histological analysis was performed on the liver, lungs and kidneys of all animals. RESULTS CNTs did not affect cell viability and their ability to differentiate in osteocytes and adipocytes. Both the CNTs and the magnetic field did not alter the cell growth rate, phenotype and cytoskeletal conformation. CNTs, when exposed to magnetic fields, are able to shepherd MSCs towards the magnetic source in vitro. Moreover, the application of a magnetic field alters the biodistribution of CNT-labelled MSCs after intravenous injection into rats, increasing the accumulation of cells into the target organ (liver). CONCLUSION Multiwalled CNTs hold the potential for use as nanodevices to improve therapeutic protocols for transplantation and homing of stem cells in vivo. This could pave the way for the development of new strategies for the manipulation/guidance of MSCs in regenerative medicine and cell transplantation.

Evaluation of T Cell Immunity against Human Cytomegalovirus: Impact on Patient Management and Risk Assessment of Vertical Transmission

Cytomegalovirus (CMV) is one of the most common infectious agents, infecting the general population at an early age without causing morbidity most of the time. However, on particular occasions, it may represent a serious risk, as active infection is associated with rejection and disease after solid organ transplantation or fetal transmission during pregnancy. Several methods for CMV diagnosis are available on the market, but because infection is so common, careful selection is needed to discriminate primary infection from reactivation. This review focuses on methods based on CMV-specific T cell reactivity to help monitor the consequences of CMV infection/reactivation in specific categories of patients. This review makes an attempt at discussing the pros and cons of the methods available.

Quantum dots labelling allows detection of the homing of mesenchymal stem cells administered as immunomodulatory therapy in an experimental model of pancreatic islets transplantation

Cell transplantation is considered a promising therapeutic approach in several pathologies but still needs innovative and non‐invasive imaging technologies to be validated. The use of mesenchymal stem cells (MSCs) attracts major interest in clinical transplantation thanks to their regenerative properties, low immunogenicity and ability to regulate immune responses. In several animal models, MSCs are used in co‐transplantation with pancreatic islets (PIs) for the treatment of type I diabetes, supporting graft survival and prolonging normal glycaemia levels. In this study we investigated the homing of systemically administered MSCs in a rat model of pancreatic portal vein transplantation. MSCs labelled with quantum dots (Qdots) were systemically injected by tail vein and monitored by optical fluorescence imaging. The fluorescence signal of the liver in animals co‐transplanted with MSCs and PIs was significantly higher than in control animals in which MSCs alone were transplanted. By using magnetic labelling of PIs, the homing of PIs into liver was independently confirmed. These results demonstrate that MSCs injected in peripheral blood vessels preferentially accumulate into liver when PIs are transplanted in the same organ. Moreover, we prove that bimodal MRI‐fluorescence imaging allows specific monitoring of the fate of two types of cells.

Entry inhibition of HSV-1 and -2 protects mice from viral lethal challenge

Abstract The present study focused on inhibition of HSV‐1 and ‐2 replication and pathogenesis in vitro and in vivo, through the selective targeting of the envelope glycoprotein D. Firstly, a human monoclonal antibody (Hu‐mAb#33) was identified that could neutralise both HSV‐1 and ‐2 at nM concentrations, including clinical isolates from patients affected by different clinical manifestations and featuring different susceptibility to acyclovir in vitro. Secondly, the potency of inhibition of both infection by cell‐free viruses and cell‐to‐cell virus transmission was also assessed. Finally, mice receiving a single systemic injection of Hu‐mAb#33 were protected from death and severe clinical manifestations following both ocular and vaginal HSV‐1 and ‐2 lethal challenge. These results pave the way for further studies reassessing the importance of HSV entry as a novel target for therapeutic intervention and inhibition of cell‐to‐cell virus transmission. HighlightsHSV‐1 and ‐2 cross‐protection is conferred in vivo by a single post‐infection systemic administration of a human anti‐gD mAb.Inhibition of HSV entry by this mAb also results in inhibition of cell‐to‐cell virus transmission.Different molecular formats (Fab, scFv and IgG) of Hu‐mAb#33 exert different anti‐viral activity.HSV‐1 and ‐2 clinical isolates are more sensitive to mAb#33 activity compared to reference virus laboratory strains.