Innovation public policies and competitiveness of the italian Industrie.

Technical and organizational innovation are crucial factors for the competitiveness of every country. Italy, characterized by a prevalence of small and medium-sized companies, generally appears more dynamic in the innovation of processes than in the innovation of products, showing a wide lack of managerial culture. One must ask if the Italian industrial structure is compatible with sustained innovative dynamism and why only very few innovative companies grow to the point of becoming important international oligopolists in their markets. In the vast majority of industrial sectors in highly industrialized countries sustained dynamic innovation is based on the coexistence of an oligopolistic core of large companies surrounded by small and medium-sized companies. In Italy the fundamental problem is the weakness of this oligopolistic core. Moreover, the financial context and the low level of managerialism of small and medium-sized companies lead to low incentives for growth and do not encourage strategies of leading to innovation. The general objectives which derive from this analysis regard: a) the need to increase the capacity of industry and to introduce innovative products, processes and systems of organization in industrial sectors b) strengthening and spreading innovative skills for technology which present high learning opportunities c) developing support structures for industrial research. In the aforesaid context, speaking of reinforcing applied research and collaboration between universities and industry assumes a great importance.

Contribution of Stem Cells to Kidney Repair

The potential role of stem cells in the repair of glomerular and tubular injury is under intensive investigation. Several studies have addressed the role of endogenous bone-marrow (BM)-derived stem cells (SC) in the repair of renal injury. Some reports indicate that BM-derived SC are capable of engraftment into damaged nephrons, although the lineage of SC recruited has not been established. However, this issue remains highly controversial, and several studies point to a paracrine/endocrine action of endogenous SC rather than a direct repopulation of the injured nephron. Administration of exogenous mesenchymal SC in experimental acute kidney injury suggests that an SC-based therapy may improve functional and structural recovery of both glomerular and tubular compartments. A contribution of renal resident SC has also been postulated in the recovery after damage. However, several points still need to be clarified regarding the signals regulating homing of SC to injured tissue, the secreted factors underlying the paracrine/endocrine mechanisms, and in particular the long-term in vivo behavior of the administered SC. This review summarizes the current literature on the physiological role of endogenous SC in renal regeneration and on the potential therapeutic strategies based on the administration of exogenous SC

Resident Stem Cells and Renal Carcinoma

According to the cancer stem cell hypothesis tumors are maintained by a cancer stem cell population which is able to initiate and maintain tumors. Tumor-initiating stem cells display stem or progenitor cell properties such as self-renewal and capacity to re-establish tumors that recapitulate the tumor of origin. In this paper, we discuss data relative to the presence of cancer stem cells in human renal carcinoma and their possible origin from normal resident stem cells. The cancer stem cells identified in human renal carcinomas are not derived from the normal CD133+ progenitors of the kidney, but rather from a more undifferentiated population that retains a mesenchymal phenotype. This population is able to self-renewal, clonogenicity, and in vivo tumor initiation. Moreover, they retain pluripotent differentiation capability, as they can generate not only the epithelial component of the tumor, but also tumor endothelial cells. This suggests that renal cancer stem cells may contribute to the intratumor vasculogenesis

Platelet-activating factor mediates CD40-dependent angiogenesis and endothelial-smooth muscle cell interaction.

The aim of the present study was to investigate whether stimulation of CD40 expressed by endothelial or smooth muscle cells triggers the synthesis of platelet-activating factor (PAF), an inflammatory mediator with angiogenic properties, and whether PAF contributes to CD40-induced neoangiogenesis. The results obtained indicate that the interaction of CD40 with soluble CD154 or with CD154 expressed on the membrane of leukocytes (CD154-transfected J558 cells) or of activated platelets, stimulated the synthesis of PAF by endothelial cells but not by smooth cells. The synthesis of PAF triggered by activated platelets was inhibited by a soluble CD40-murine Ig fusion protein that prevents the interaction between membrane CD40 and CD154. Studies with specific inhibitors and evaluation of protein phosphorylation indicated the involvement in PAF synthesis of two intracellular signaling pathways leading to cytosolic phospholipase A 2 activation: a phospholipase Cγ-protein kinase C-Raf-p42/p44-mitogen-activated protein kinase (MAPK) and a MAPK kinase-3/6-dependent activation of p38 MAPK. PAF synthesized by endothelial cells after CD40 stimulation was instrumental in the in vitro migration and vessel-like organization of endothelial cells, and in the interaction between endothelial cells and smooth muscle cells, as inferred by the inhibitory effect of two different PAF receptor antagonists, WEB2170 and CV3988. In vivo, blockade of PAF receptors prevented the angiogenic effect triggered by CD40 stimulation in a murine model of s.c. Matrigel implantation. In conclusion, these observations indicate that PAF synthesis induced by stimulation of endothelial CD40 contributes to the formation and organization of new vessels. This may be relevant in the vascular remodeling associated with tumor and inflammatory neoangiogenesis

Human CD133 + Renal Progenitor Cells Induce Erythropoietin Production and Limit Fibrosis after Acute Tubular Injury

Persistent alterations of the renal tissue due to maladaptive repair characterize the outcome of acute kidney injury (AKI), despite a clinical recovery. Acute damage may also limit the renal production of erythropoietin, with impairment of the hemopoietic response to ischemia and possible lack of its reno-protective action. We aimed to evaluate the effect of a cell therapy using human CD133(+) renal progenitor cells on maladaptive repair and fibrosis following AKI in a model of glycerol-induced rhabdomyolysis. In parallel, we evaluated the effect of CD133(+) cells on erythropoietin production. Administration of CD133(+) cells promoted the restoration of the renal tissue, limiting the presence of markers of injury and pro-inflammatory molecules. In addition, it promoted angiogenesis and protected against fibrosis up to day 60. No effect of dermal fibroblasts was observed. Treatment with CD133(+) cells, but not with PBS or fibroblasts, limited anemia and increased erythropoietin levels both in renal tissue and in circulation. Finally, CD133(+) cells contributed to the local production of erythropoietin, as observed by detection of circulating human erythropoietin. CD133(+) cells appear therefore an effective source for cell repair, able to restore renal functions, including erythropoietin release, and to limit long term maldifferentiation and fibrosis