Nico van Rooijen

Publications (3)14.82 Total impact

• Article: Macrophage depletion following liposomal-encapsulated clodronate (LIP-CLOD) injection enhances megakaryocytopoietic and thrombopoietic activities in mice.

  Fernanda Alves-Rosa, Mónica Vermeulen, Juana Cabrera, Carmen Stanganelli, Alejandra Capozzo, Marina Narbaitz, Nico van Rooijen, Marina Palermo, Martín A Isturiz
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  ABSTRACT: Megakaryocytopoiesis is the cellular process by which stem cells progress through commitment, proliferation and differentiation, leading to the production of platelets. In the mouse, this process is accomplished within the bone marrow (BM) and spleen microenvironment and is carried out by regulatory molecules and accessory cells, including macrophages, fibroblasts and endothelial-like cells. Previously, we demonstrated that specific macrophage depletion, using liposomal-encapsulated clodronate (LIP-CLOD), induced a rapid recovery of the platelet count in a mouse model of immune thrombocytopenia. We now show that LIP-CLOD treatment also provoked enhancement of both megakaryocytopoiesis and thrombocytopoiesis. In fact, a dose-dependent increase in the number of BM and spleen megakaryocytes was detected after treatment and this pattern correlated inversely to the macrophage count detected in these organs. Furthermore, the mice treated with the higher dose of LIP-CLOD showed signs of enhanced thrombopoiesis as they had an increased frequency of reticulated platelets and an improvement in the total platelet count 2 d later. In addition, the in vitro cytokine-induced megakaryocytopoiesis in BM and spleen cell cultures was significantly augmented in the presence of LIP-CLOD. Taken together, these results suggest that BM and spleen microenvironmental macrophages could be involved in the regulation of megakaryocyte and platelet production.
  British Journal of Haematology 05/2003; 121(1):130-8. · 4.94 Impact Factor
• Article: Macrophage depletion following liposomal‐encapsulated clodronate (LIP‐CLOD) injection enhances megakaryocytopoietic and thrombopoietic activities in mice

  Fernanda Alves-Rosa, Mónica Vermeulen, Juana Cabrera, Carmen Stanganelli, Alejandra Capozzo, Marina Narbaitz, Nico Van Rooijen, Marina Palermo, Martín A. Isturiz
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  ABSTRACT: Megakaryocytopoiesis is the cellular process by which stem cells progress through commitment, proliferation and differentiation, leading to the production of platelets. In the mouse, this process is accomplished within the bone marrow (BM) and spleen microenvironment and is carried out by regulatory molecules and accessory cells, including macrophages, fibroblasts and endothelial-like cells. Previously, we demonstrated that specific macrophage depletion, using liposomal-encapsulated clodronate (LIP-CLOD), induced a rapid recovery of the platelet count in a mouse model of immune thrombocytopenia. We now show that LIP-CLOD treatment also provoked enhancement of both megakaryocytopoiesis and thrombocytopoiesis. In fact, a dose-dependent increase in the number of BM and spleen megakaryocytes was detected after treatment and this pattern correlated inversely to the macrophage count detected in these organs. Furthermore, the mice treated with the higher dose of LIP-CLOD showed signs of enhanced thrombopoiesis as they had an increased frequency of reticulated platelets and an improvement in the total platelet count 2 d later. In addition, the in vitro cytokine-induced megakaryocytopoiesis in BM and spleen cell cultures was significantly augmented in the presence of LIP-CLOD. Taken together, these results suggest that BM and spleen microenvironmental macrophages could be involved in the regulation of megakaryocyte and platelet production.
  British Journal of Haematology 03/2003; 121(1):130 - 138. · 4.94 Impact Factor
• Article: Rapid recovery of platelet count following administration of liposome-encapsulated clodronate in a mouse model of immune thrombocytopenia.

  Fernanda Alves-Rosa, Carmen Stanganelli, Juana Cabrera, Dora Cymberknop, Carolina Rubel, Silvia Vanzulli, Nico van Rooijen, Marina Palermo, Martín A Isturiz
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  ABSTRACT: Immune thrombocytopenic purpura (ITP) is a haematological disorder characterized by increased platelet consumption. The destruction of platelets is mediated by the reticulo-endothelial system (RES), particularly by splenic and hepatic macrophages. Previously, we demonstrated in a mouse model of thrombocytopenia that the depletion of these cells by liposome-encapsulated clodronate (LIP-CLOD) induces the recovery of the platelet count. We now report that LIP-CLOD is capable of reversing the thrombocytopenia with minimal effects on both, functional RES integrity and platelet functionality. Our data indicate that thrombocytopenic mice treated with low doses of LIP-CLOD/body weight increase the platelet count to haemostatically safe values within 18 h of treatment. The predictable bleeding time was significantly decreased in these mice, suggesting that the circulating platelets have enhanced haemostatic capacity. Platelet functionality measured through the ADP-induced fibrinogen-binding assay showed normal platelet activation after treatment. Regarding immunological competence, mice treated with LIP-CLOD showed similar antibody titres against sheep red blood cells. However, antibody-dependent cell-mediated cytotoxicity carried out by splenocytes was reduced. All these data demonstrate that LIP-CLOD deserves consideration as a potential therapeutic approach in thrombocytopenic states in which the rapid increase of platelet count is the primary goal.
  British Journal of Haematology 03/2002; 116(2):357-66. · 4.94 Impact Factor