Electrospun poly(lactic acid) membranes with defined pore size to enhance cell infiltration.

Electrospun membranes are compact structures with small pore sizes that hinder cell infiltration, resulting in membranes with cells attached only to the external surface rather than throughout the entire volume. Thus, there is a need to increase the pore size of electrospun membranes maintaining their structural similarity to the extracellular matrix. In this work, we used glucose crystals embedded in polyethylene oxide (PEO) fibers to create large pores in poly(lactic acid) (PLA) electrospun membranes to allow for cellular infiltration. The PEO fibers containing glucose crystals of different sizes (>50, 50-100 and 100-150 µm) and in varying concentrations (10, 15 and 20 %) were co-electrospun with PLA fibers and subsequently leached out using distilled water. PLA fibrous membranes without glucose crystals were also produced as controls. The membranes were examined for their morphology, mechanical properties, and potential to support the proliferation of fibroblasts. In addition, the immune response to the membranes was evaluated using monocyte-derived macrophages. The glucose crystals were uniformly distributed in the PLA membranes and their removal created open pores without collapsing the structure. Although a reduced Young's modulus was observed for membranes produced using higher glucose crystal concentrations and larger crystal sizes, the structural integrity remained intact, and the values are still suitable for tissue engineering. In vitro results showed that the scaffolds supported the adhesion and proliferation of fibroblasts and the pores created in the PLAmembranes were large enough for fibroblasts infiltration and colonization of the entire scaffold without inducing an inflammatory response.

The Production Processes and Biological Effects of Intravenous Immunoglobulin.

Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it can stimulate certain sub-populations of T cells with effects on T cell proliferation, survival and function in situations of lymphopenia. These results present a novel and considerable impact of intravenous immunoglobulin (IVIg) treatment in situations of severe lymphopenia, a situation that can occur in cancer patients after chemo and radiotherapy treatments. In this review paper the established and experimental role of polyclonal immunoglobulin will be presented and discussed as well as the manufacturing processes involved in their production.

Treatment with polyclonal immunoglobulin during T-cell reconstitution promotes naive T-cell proliferation.

Natural antibodies are unique self molecules endowed with both suppressive and activating functions on various cells of the immune system and are recognized as a fundamental link between the adaptive and innate immune system. Here, we examine the role of natural antibodies, using polyclonal immunoglobulins (Ig), as a promoter of T-cell reconstitution in a context of lymphopenia. We have established a mouse model to mimic immunologic recovery in adult patients with severe hypothymic function subjected to autologous hematopoietic precursor cell transplantation. Thymectomized mice were transplanted and treated with low doses of Ig or its Fab or Fc fragments. The animals displayed, during early phases of Ig treatment, a significant increase of T-cell reconstitution displaying a naive CD4(+) phenotype. In addition, the Ig-treated animals exhibited an increase dilution of single-joint T-cell receptor excision circles (sjTRECs) in peripheral blood, suggesting an early increase in proliferation of T cells stimulated by the natural antibodies. These results unveil a novel and considerable effect of intravenous Ig treatment in situations of severe lymphopenia as a stimulator of proliferation of peripheral naive T cells, possibly protecting diverse immune repertoires.