Connexin-43 in the osteogenic BM niche regulates its cellular composition and the bidirectional traffic of hematopoietic stem cells and progenitors

Connexin-43 (Cx43), a gap junction protein involved in control of cell proliferation, differentiation and migration, has been suggested to have a role in hematopoiesis. Cx43 is highly expressed in osteoblasts and osteogenic progenitors (OB/P). To elucidate the biologic function of Cx43 in the hematopoietic microenvironment (HM) and its influence in hematopoietic stem cell (HSC) activity, we studied the hematopoietic function in an in vivo model of constitutive deficiency of Cx43 in OB/P. The deficiency of Cx43 in OB/P cells does not impair the steady state hematopoiesis, but disrupts the directional trafficking of HSC/progenitors (Ps) between the bone marrow (BM) and peripheral blood (PB). OB/P Cx43 is a crucial positive regulator of transstromal migration and homing of both HSCs and progenitors in an irradiated microenvironment. However, OB/P Cx43 deficiency in nonmyeloablated animals does not result in a homing defect but induces increased endosteal lodging and decreased mobilization of HSC/Ps associated with proliferation and expansion of Cxcl12-secreting mesenchymal/osteolineage cells in the BM HM in vivo. Cx43 controls the cellular content of the BM osteogenic microenvironment and is required for homing of HSC/Ps in myeloablated animals

MMonCa: A flexible and powerful new Kinetic Monte Carlo simulator

Kinetic Monte Carlo (KMC) is a widely used technique to simulate the evolution of radiation damage inside solids. Despite de fact that this technique was developed several decades ago, there is not an established and easy to access simulating tool for researchers interested in this field, unlike in the case of molecular dynamics or density functional theory calculations. In fact, scientists must develop their own tools or use unmaintained ones in order to perform these types of simulations. To fulfil this need, we have developed MMonCa, the Modular Monte Carlo simulator. MMonCa has been developed using professional C++ programming techniques and has been built on top of an interpreted language to allow having a powerful yet flexible, robust but customizable and easy to access modern simulator. Both non lattice and Lattice KMC modules have been developed. We will present in this conference, for the first time, the MMonCa simulator. Along with other (more detailed) contributions in this meeting, the versatility of MMonCa to study a number of problems in different materials (particularly, Fe and W) subject to a wide range of conditions will be shown. Regarding KMC simulations, we have studied neutron-generated cascade evolution in Fe (as a model material). Starting with a Frenkel pair distribution we have followed the defect evolution up to 450 K. Comparison with previous simulations and experiments shows excellent agreement. Furthermore, we have studied a more complex system (He-irradiated W:C) using a previous parametrization [1]. He-irradiation at 4 K followed by isochronal annealing steps up to 500 K has been simulated with MMonCa. The He energy was 400 eV or 3 keV. In the first case, no damage is associated to the He implantation, whereas in the second one, a significant Frenkel pair concentration (evolving into complex clusters) is associated to the He ions. We have been able to explain He desorption both in the absence and in the presence of Frenkel pairs and we have also applied MMonCa to high He doses and fluxes at elevated temperatures. He migration and trapping dominate the kinetics of He desorption. These processes will be discussed and compared to experimental results. [1] C.S. Becquart et al. J. Nucl. Mater. 403 (2010) 75